IASLC Lung Cancer News - V5, N3

U.S. EDITION

V5 / N3 / JUNE 2020

FOR THORACIC ONCOLOGY SPECIALISTS Read online at LungCancerNews.org g and visit IASLC.org

INSIDE AACR Coverage (More online!)

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TRACERx: Tracking MRD With ctDNA Heralds Disease Relapse

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cfDNA Analysis Suggests EML4-ALK Variant Does Not Influence Response to Lorlatinib

Telehealth Series: Success and Challenges

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Telehealth Is Not a One-Size-Fits-All Approach

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Losing the Personal Touch in the Digital World

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Patient, Provider Safety Paramount During Pandemic

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Telehealth Can Be a Patient-First Approach

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Broad Molecular Testing in Lung Cancer: The Struggle to Translate Recommendations to Clinical Practice

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Making Mesothelioma Patient Research Happen: The UK Experience

E V O LV I N G S TA N D A R D S O F C A R E

Sublobar Resections for Early Lung Cancer

By Tetsuya Mitsudomi, MD

The general principle of surgery for cancer of any organ is to remove the entire tumor with adequate margins of normal tissue along with regional lymph nodes that may have the potential for metastatic spread, even if preoperative imaging studies do not indi-

cate any signs of metastases. The lung is composed of lobes, and each lobe is composed of segments. Therefore, there are several potential operative procedures for lung cancer, depending on the amount of lung parenchyma to be removed (Fig. 1). Segmentectomies and wedge resections (also called partial resections) are often referred to as

Fig. 1. Varieties of Pulmonary Resections According to the Amount of Lung Parenchyma to Be Removed

Perspectives on TTFields in Unresectable MPM

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STELLAR Results in Practice

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STELLAR: More Stars Needed in the Constellation

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Lung Cancer in the Brazilian Health System

sublobar or limited resections. Wedge resections are also referred to as nonanatomical resections, in contrast to other resections that remove at least one segment of the lung taking the bronchovascular anatomy into consideration.

Pneumonectomy to Lobectomy as a Standard Procedure The first long-term survival after lung cancer surgery was achieved in 1933 by Graham and Singer,1 who performed a left pneumonectomy for a 48-year-old male gynecologist. The patient survived for 30 years after surgery. In 1950, Churchill2 at the Massachusetts General Hospital reported that 30-day mortality for pneumonectomies and lobectomies for lung cancer during 1933-1950 was 23% and 14%, respectively, with 5-year survival rates of 12% and 19%, respectively, suggesting that lobectomies might be safer with better long-term survival compared with pneumonectomies. In the 1950s, pneumonectomy, however, was regarded as a standard of continued on page 2

E V O LV I N G S TA N D A R D S O F C A R E

Evolution of Patient-Reported Outcomes in Lung Cancer: A Q&A With Dr. Benjamin Movsas The IASLC Lung Cancer News spoke with B enjamin Movsas, MD, regarding the evolution of patient-reported outcomes (PROs) for lung cancer. Dr. Movsas is the co-chair of the PatientCentered Outcomes Research Committee for the NRG Oncology Cooperative Group, chair of the radiation oncology department at the Henry Ford Cancer Institute in Michigan, and an expert in radiation oncology, lung and prostate cancers, and quality-of-life issues related to cancer. After 2 decades of involvement in PRO-based research, Dr. Movsas now sees quality of life as “a new vital sign” with a profound impact on clinical decisions.

Q: How can quality-of-life PROs be implemented into clinical trials in a standardized way?

A: When it comes to clinical trials incorporating quality of life, the key issue— just as it is with any other trial—is that its use needs to be hypothesis driven.

Just as in comparing two treatments, the hypothesis regarding how quality of life differs between arms is the driving factor. That is important because the anticipated differences in quality of life between the arms of a trial will determine which validated instrument will best be able to show whether that difference is real using a “clinically meaningful change.” Then, of course, the appropriate statistics, design, and patient population need to be considered.

There are many validated is an extremely important PRO instruments. For issue. PRO data cannot example, the European be obtained retrospecOrganis ation for tively, so the design Research and of the study is very Treatment of Cancer important to ensure has many validated compliance.

For example, in a instruments, both lung cancer study,1 we generic and specific to Dr. Benjamin Movsas lung cancer. There also decided not to use the full FACT-Lung instrument, is the validated Functional Assessment of Cancer Therapy (FACT) which is approximately 30 to 40 quesinstrument. These instruments are avail- tions. Instead, we used a shorter valiable in multiple languages. These are dated subscale called the FACT-Trials great places to start, but it should not be Outcome Index (TOI); the FACT-TOI one size fits all; investigators might want focuses on physical and functional wellto pick a specific instrument based on being, as well as the lung cancer symptheir hypothesis. If we ask too much of tom subscale. It consists of approxiour patients, we risk missing data, which continued on page 3

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IASLC LUNG CANCER NEWS / JUNE 2020

Sublobar Resections

276 patients were randomized to the from page 1 trial arms; however, only 247 were analyzed due to protocol violations. The care when big surgery was assumed to local recurrence rate was 3-fold higher yield maximal chance of cure, as exem- in the limited resection group complified by Halsted’s radical mastectomy. pared to the lobectomy group (5.4%/ In 1962, Shimkin et al.,3 at the biometry person/year vs. 1.9%), whereas there branch of the National Cancer Institute, was no difference in distant recurrence retrospectively compared the survival rates.7 In addition, OS was longer in of 116 cases of lung cancer treated by the lobectomy group with a one-sided lobectomy with 402 cases treated by p-value of 0.062.7 Limited pulmonary pneumonectomy. They reported that resection also failed to confer improved lobectomies resulted in at least equiva- perioperative morbidity or mortality, or lent prognosis for either those reduction in late postoperative with localized or noncomplications.7 Therefore, 3 localized disease. In the authors concluded accordance with these that lobectomy was still data, lobectomies the surgical procedure of choice for patients gradually became with peripheral T1N0 the standard procedure. For example, NSLC. However, this at the Massachusetts paper carried several General Hospital, the flaws in that there was Dr. Tetsuya Mitsudomi no significant difference if percentages of pneumoall randomized patients were nectomies in total lung analyzed and that pulmonary funcresection decreased from 57% in 1931-1940 to 11% in 1961-1970. 4 tion tests were not systematically comMore recently, it was reported that of pleted, as pointed out in accompanying 79,953 patients who underwent pneu- commentaries. However, lobectomy has monectomy or lobectomy for lung remained the standard of care based in cancer between 2004 and 2013, only 5% large part on this paper because this was had pneumonectomy according to the the only phase III randomized study at National Cancer Database.5 The 5-year that time to address this issue. unadjusted survival rates were 46% and Since then, limited resections for 60% for pneumonectomy and lobec- NSCLC are “officially” indicated only for tomy, respectively.5 In Japan, pneumo- very early-stage tumors or for patients nectomy only accounted for 1.8% of with functional organ impairment who 18,073 pulmonary resections for lung would not tolerate lobectomies. The syscancer performed in 2010.6 tematic quantitative review analyzing 53 non-randomized studies and the aforeSublobar Resections as a mentioned LCSG study showed that Therapeutic Option there was no difference in OS between Many patients with lung cancer do not lobectomies and sublobar resections in tolerate lobectomies because they are patients intentionally selected by oncooften older with impaired physiologic logic features of the tumor, but that reserves due to coexisting morbidities there was a significantly worse outcome (e.g., chronic obstructive lung disease) in the patients undergoing sublobar which is often related to tobacco smok- resections because of their poor funcing. In addition, when the tumor is very tional reserve.8 small, it might not be necessary to remove an entire lobe. Therefore, it is tempting to Postoperative Complications consider sublobar resections for selected and Pulmonary Functions patients. Jensik et al.6 reported the early After Sublobar Resections results of segmentectomies for lung Although the LCSG study did not show cancer with a 5-year survival rate of 56% improvement in pulmonary function in in 69 patients undergoing curative resec- the sublobar group, Okada et al.9 showed tion. With the advent of the CT scanner that sublobar resection for tumors 2 cm in the late 1970s, it became possible to or smaller resulted in similar survival detect smaller lung cancers, which fur- outcomes, yet significantly better postther promoted the wave toward these operative pulmonary function comtissue-sparing resections. pared with patients who underwent The Lung Cancer Study Group lobectomies in their prospective non(LCSG), led by Robert J. Ginsberg, randomized study. Postoperative acute MD,7 performed a randomized trial exacerbation (AE) of interstitial lung comparing lobectomies with limited disease (ILD) is one of the main causes resection for stage I lung cancer (tumor of postoperative mortality following diameter ≤ 3 cm without lymph node pulmonary resections for lung cancer. metastases; LCSG 821). In this study, In a large retrospective analysis of 1,763

patients with ILD w ho under went pulmonary resections, larger surgical procedures were significantly associated with greater chance of AE (odds ratio of lobectomy/ segmentectomy compared to wedge resection was 3.83; p < 0.001).10

Fig. 2. Lung Cancer Manifested as Ground Glass Nodules and Definition of C/T Ratio

Abbreviations: C/T ratio, ratio of the diameter of a consolidated part (non-ground glass) to that of the total tumor.

Technical Considerations As mentioned earlier, it is important to secure an adequate margin of intact tissue in cancer surgery of any organ.

With respect to lung cancer procedures, difficulties for securing such margins depend on the size as well as depth of the tumor from the surface of the lung.

This is because the lung structure is understood as a collection of pyramidshaped segments with their bottoms located toward the surface of the lung and with their apices toward the pulmonary hilum. Therefore, the deeper and the bigger a tumor is, the more difficult it will be to perform “adequate” sublobar resections, especially wedge resections.

Indeed, in retrospective studies, it has been shown that tumors larger than 2 cm have a higher local recurrence rate.11

Role of Ground-Glass Appearance on CT for Selection of Patients for Sublobar Resections However, it has often been observed that even a small tumor less than 2 cm may show aggressive tumor behavior. In 1995, Noguchi12 reported the subclassification of the adenocarcinoma of the lung less than 2 cm according to histologic findings. In Noguchi’s classification, type A, which featured replacement growth of alveolar-lining epithelial cells with a relatively thin stroma, and type B (type A with foci of structural collapse of alveoli) yielded a 100% 5-year survival rate.12 With the great improvement in the resolution of modern CT imaging, a tumor with this replacement growth manifests as a nodule with a pale radioopaque shadow resembling frosted glass.

These are called ground glass nodules (GGN). GGN can be inflammatory; however, if such shading persists for a long period of time over serial scans, it is very likely to be early lung adenocarcinoma without invasion.13,14 In several retrospective studies, it was proposed that the ratio of the diameter of a consolidated part (non–ground glass) to that of a total tumor (C/T ratio) was associated with patient prognosis

(Fig. 2). The Japan Clinical Oncology Group (JCOG) 0201 study prospectively showed that when radiologic invasiveness was defined as tumor diameter less than 2 cm with C/T ratio less than either 25% or 50%, 99% and 96% of tumors, respectively, were pathologically noninvasive, defined as the absence of invasion into blood vessels, lymphatics, and pleura or lymph node metastases.15 As expected, patients with tumors with C/T less than 25% had excellent survival outcomes, with a 5-year recurrencefree survival rate of 97% when treated by lobectomy.16 Following this study, sublobar resections (mainly wedge resections) for these radiologically noninvasive lung cancers were prospectively examined in the JCOG0802 study. 17 The 5-year recurrence-free survival for these 314 patients was 99.7% (95% CI [97.7%, 100.0%]) with no local relapses recorded.17 To further expand the indication of sublobar resections for lung cancer, the JCOG, in a prospective, randomized trial, is now comparing lobectomies to segmentectomies for tumors 2 cm or smaller and a C/T ratio greater than 50% (JCOG0802/WJOG4607L). Patient accrual has completed, and data maturation are awaited. Similarly, CALGB 14503 is a randomized controlled trial comparing lobectomies to segmentectomies/wedge resection for peripheral NSCLC 2 cm or smaller in diameter with no evidence of lymph node metastases.

Conclusion Lobectomy remains the standard of care for pulmonary resection for lung cancer.

However, sublobar resections are a reasonable option for selected patients with early lung cancer. According to the latest version of the National Comprehensive Cancer Network guideline, segmentectomies or wedge resections are considered appropriate for patients who would not tolerate lobectomies due to comorbidity or for those with peripheral nodules 2 cm or smaller with at least one of the following features: continued on page 3

LUNGCANCERNEWS.ORG / JUNE 2020

Evolution of Research Using PROs from page 1

mately 20 questions and takes only approximately 5 minutes to complete, which helped with patient compliance.

The FACT-TOI also has pre-determined values for defining clinically meaningful changes, so it provides researchers with pre-defined metrics to look for in the data.

Q: Can you explain the key role of PROs in lung cancer?

A: There are a number of research studies from the past 2 decades that show quality of life to be a very powerful prognostic factor. In one analysis in which I was involved, we looked at patients with stage III NSCLC who were receiving chemoradiation, and baseline quality of life was found to be the most important prognostic factor for survival.2 This remains true even 5 years after the study’s completion. Although we have traditional prognostic factors that we use all of the time in the clinic, it would be very helpful to add quality of life to that list because it will better guide our clinical decisions.

Indeed, multiple studies in various cancer settings have shown that PROs tend to be more sensitive than other outcome measures, such as clinical toxicity measures.3 So if a physician is trying to determine the benefit of a new technology, he or she may have the ability to detect more subtle but clinically meaningful differences using PROs. For example, in RTOG 0617, while this study was not randomized to compare 3-D conformal radiation (3-D CRT) versus intensity-modulated radiation therapy (IMRT), overall the patients were reasonably well balanced, and almost half were treated with each technique.

Sublobar Resections from page 2

1) pure adenocarcinoma in situ, 2) C/T ratio 50% or less, or 3) radiologically surveyed long tumor doubling time of 400 days or greater.18 ✦ About the Author: Dr. Mitsudomi is President of the IASLC and a professor in the Department of Thoracic Surgery, Kindai University Faculty of Medicine, Japan.

Please note that the full reference list for this article appears online at lungcancernews.org.

References: 1. Graham EA, Singer JJ. Successful removal of an entire lung for carcinoma of the bronchus. JAMA. 1933;101(4):1371-1374.

2. Churchill ED, Sweet RH, Soutter L, et al. The

Although there were not many differences between standard toxicity measures for the two techniques, the patients who received IMRT (vs. 3-D CRT) had a relative clinically meaningful improvement in quality of life 1 year post-therapy. It was pretty dramatic in that almost half of the patients who received 3-D CRT had a clinically meaningful decline, but only a quarter of patients who received IMRT showed the same decline.1

come full circle in that, in the past, we were excited about the idea that PROs helped us to prognosticate for survival; not only did that happen, but identifying and acting on PROs in real time actually helps us improve survival itself. A recent study in metastatic lung cancer showed the same results as the all-cancers study.5 If we had an expensive novel drug that showed the same increase in survival, we would probably be using it. Now that we

Now that we have this highly cost-effective real-time PRO approach that achieves a significant survival improvement, this justifies moving quality of life from research into the clinic.

What is most exciting to me is that we are starting to really get a sense that PROs can directly impact and potentially increase survival itself, which is truly amazing. Ethan Basch, MD, and colleagues performed a recent study of more than 700 patients with stage IV cancers of various kinds who were receiving chemotherapy. Patients in this study were randomly divided into two groups: one group reported symptoms using traditional in-clinic methods, and the other had real-time PRO reporting via a tablet or email communication with nurses.

Results showed that patients in the realtime PRO group not only had better quality of life, which was expected, but those patients also had fewer emergency department visits (34% vs. 41% for traditional reporting). These patients were more compliant with chemotherapy and had increased survival rates compared to patients who were not reporting symptoms in real time. So not only did patients who participated in the real-time PRO receive more therapy with better quality of life, but they lived longer, and cost of care with respect to emergency department visits was decreased.4 It seems that the research on PROs has

have this highly cost-effective real-time PRO approach that achieves a significant survival improvement, this justifies moving quality of life from research into the clinic.

surgical management of carcinoma of the lung; a study of the cases treated at the Massachusetts General Hospital from 1930 to 1950. J Thorac Surg. 1950;20(3):349-365.

3. Shimkin MB, Connelly RR, Marcus SC, et al.

Pneumonectomy and lobectomy in bronchogenic carcinoma. A comparison of end results of the Overholt and Ochsner clinics. J Thorac Cardiovasc Surg. 1962;44:503-519.

4. Wilkins EW, Jr., Scannell JG, Craver JG. Four decades of experience with resections for bronchogenic carcinoma at the Massachusetts General Hospital. J Thorac Cardiovasc Surg.

1978;76(3):364-368.

4a. Dhanasopon AP, Salazar MC, Hoag JR, et al. Fate of Pneumonectomy Patients Variably Captured

by Non-Small Cell Lung Cancer Staging System.

Ann Thorac Surg 104:1829-1836, 2017 4b Okami J, Shintani Y, Okumura M, , et al.

Demographics, Safety and Quality, and Prognostic Information in Both the Seventh and Eighth Editions of the TNM Classification in 18,973 Surgical Cases of the Japanese Joint Committee of Lung Cancer Registry Database in 2010. J Thorac Oncol 14:212-222, 2019 5. Jensik RJ, Faber LP, Milloy FJ, et al. Segmental resection for lung cancer. A fifteen-year experi-

ence. J Thorac Cardiovasc Surg. 1973;66(4):563572.

6. Ginsberg RJ, Rubinstein LV. Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group. Ann Thorac Surg. 1995;60(3):615-622; discussion 622-623.

7. Cao C, Chandrakumar D, Gupta S, et al. Could less be more?-A systematic review and meta-analysis of sublobar resections versus lobectomy for non-small cell lung cancer according to patient selection. Lung Cancer. 2015;89(2):121-132.

8. Okada M, Koike T, Higashiyama M, et al. Radical sublobar resection for small-sized non-small cell lung cancer: a multicenter study. J Thorac Cardiovasc Surg. 2006;132(4):769-775.

9. Sato T, Teramukai S, Kondo H, et al. Impact and predictors of acute exacerbation of interstitial lung diseases after pulmonary resection for lung cancer. J Thorac Cardiovasc Surg.

2014;147(5):1604-1611 e3.

10. Okada M, Nishio W, Sakamoto T, et al. Effect of tumor size on prognosis in patients with nonsmall cell lung cancer: the role of segmentectomy as a type of lesser resection. J Thorac Cardiovasc Surg. 2005;129(1):87-93.

Q: Are there commercial products in the works for this?

A: A number of companies are working on web-based products that make it possible for patients to relay information to care providers in real time. Some of the products even allow for real-time back and forth with patients. For example, if the patient is having diarrhea, their web-based system can provide a recommendation immediately; if that does not work, the patient can feed this back to the care team in real time for other recommendations.

Q: Where do you see PRO research going in the future?

A: There appear to be some fascinating links between genetics and quality of life. The GENEQOL Consortium, for example, is conducting some really interesting studies evaluating genetics and fatigue, wellness, and happiness.6 Clearly, quality of life is influenced by

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our environment and life events, but it may also, at some level, be influenced by our underlying genetics. ✦ References: 1. Movsas B, Hu C, Sloan J, et al. Quality of Life Analysis of a Radiation Dose-Escalation Study of Patients With Non-Small-Cell Lung Cancer: A Secondary Analysis of the Radiation Therapy Oncology Group 0617 Randomized Clinical Trial.

JAMA Oncol. 2016;2(3):359-367.

2. Movsas B, Moughan J, Sarna L, et al. Quality of life supersedes the classic prognosticators for long-term survival in locally advanced nonsmall-cell lung cancer: an analysis of RTOG 9801.

J Clin Oncol. 2009;27(34):5816-5822.

3. Siddiqui F, Liu AK, Watkins-Bruner D, Movsas B. Patient-reported outcomes and survivorship in radiation oncology: overcoming the cons. J Clin Oncol. 2014;32(26):2920-2927.

4. Basch E, Deal AM, Dueck AC, et al. Overall Survival Results of a Trial Assessing PatientReported Outcomes for Symptom Monitoring During Routine Cancer Treatment. JAMA. 2017;318(2):197-198.

5. Denis F, Basch E, Septans AL, et al. Two-Year Survival Comparing Web-Based Symptom Monitoring vs Routine Surveillance Following Treatment for Lung Cancer. JAMA. 2019;321(3): 306-307.

6. Sprangers MA, Sloan JA, Veenhoven R, et al. The establishment of the GENEQOL consortium to investigate the genetic disposition of patientreported quality-of-life outcomes. Twin Res Hum Genet. 2009;12(3):301-311.

LUNGCANCERNEWS.ORG

VIEW ADDITIONAL CONTENT ONLINE Drs. Marina Garassino and Leora Horn provide a detailed look at the TERAVOLT Registry data and its creation. Dr. Garassino’s AACR presentation showed an “unexpectedly high” mortality rate for patients with lung cancer who had COVID-19.

Perspectives on the “new normal” of the COVID-19 era: the pros and cons of telehealth. Drs. Sandip Patel, Martin Edelman, TELEHEALTH Robert Ramirez, and Luis SUCCESSES Raez, as well as two patients, & CHALLENGES Laura Shanahan and Bonnie Anderson, offer perspectives on the challenges and benefits.

Despite policy decisions that are still pending in many countries, Dr. Brendon Stiles posits that the NELSON and NLST data are convincing regarding wide adoption of screening.

Trial data can help inform change to standard of care, but at what point do we say enough data is enough and move forward with combination therapy as the new standard of care?

Dr. Mariano Provencio compares strategies and discusses pending trials.

FDA News: A new readyto-dilute formulation of pemetrexed formulation was approved

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IASLC LUNG CANCER NEWS / JUNE 2020

MEETING NEWS

TRACERx Data Show That Tracking MRD With ctDNA Heralds Disease Relapse Kara Nyberg, PhD

New findings from the TRACERx lung study underscore the value of using circulating tumor DNA (ctDNA) to predict NSCLC relapse postsurgery based on the detection of minimal residual disease (MRD). Moreover, the results appear

sufficiently robust to begin to support use of ctDNA as a biomarker for MRD, and hence disease relapse, in the clinical setting.

“We now think that the technology is getting to the point at which we can start to leverage these biomarkers in clinical trials to direct or escalate

adjuvant treatment,” remarked Chris Abbosh, MD, of the University College London, who presented the latest TRACERx findings.

The TRACERx research initiative aims to track the genetic evolution of lung cancer from diagnosis through to relapse in individual patients. “If we want to

THE EVOLVING TREATMENT LANDSCAPE OF LUNG CANCER:

Expert Updates on the Role of Immunotherapy Increase your knowledge of the role of immunotherapy in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) by attending a 60-minute Expert Video Series titled, “The Evolving Treatment Landscape of Lung Cancer: Expert Updates on the Role of Immunotherapy.”

Dr. Giorgio Scagliotti

Drs. Giorgio Scagliotti, Enriqueta Felip, Lauren Byers, Heather Wakelee and Luis Paz-Ares share their expertise in the importance of immunotherapy and biomarkers, clinical trial data with checkpoint inhibitors in metastatic NSCLC, emerging data on checkpoint inhibitors in SCLC, and the evolving role of checkpoint inhibitors in early stage NSCLC. Oncologists, pulmonologists, pathologists, radiation oncologists, and surgeons are encouraged to participate. Valid for 1.00 AMA PRA Category 1 Credit(s)™ or for 1.00 ABIM MOC points through: 11/12/2020 This series was sponsored by Medscape and is supported by independent educational grants received by Medscape from Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Disclosure: Medscape, LLC designates this enduring material for a maximum of 1.0 AMA PRA Category 1 Credit(s)™ . Physicians should claim only the credit commensurate with the extent of their participation in the activity. Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 1.0 MOC points in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. To receive AMA PRA Category 1 Credit™, you must receive a minimum score of 75% on the post-test. Aggregate participant data will be shared with commercial supporters of this activity. For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact CME@medscape.net.

AACR

COVERAGE improve outcomes further in NSCLC, we need to focus on innovation in the earlystage space. …Driven by this need, we’ve been extensively investigating MRD in TRACERx,” Dr. Abbosh said.

The TRACERx team uses what they call “a tumor-informed personalized cell-free DNA enrichment approach” for MRD detection. In the current study, they first performed deep sequencing of primary tumors removed from 78 patients with stage I-III NSCLC. Variants for MRD tracking were prioritized to optimize MRD sensitivity at low mutant allele frequencies and enable phylogenetic tracking.

Thereafter, anchored-multiplex PCR enrichment panels were individually generated for each patient targeting a median of 196 (range 72-482) clonal and subclonal variants of interest detected in the primary tumor.

The patient-specific ctDNA enrichment panels demonstrated impressive sensitivity and specificity, detecting variant fractions as low as 0.003% of the total DNA sample. Analysis of 271 postoperative ctDNA samples taken periodically from 37 individuals without disease relapse showed that 269 of the samples—more than 99%—were MRD negative. There was a single exception among the 26 patients with no evidence of clinical relapse, which was linked to an individual who had not yet undergone adjuvant radiotherapy, and that likely reflected delayed clearance of residual disease. The other exception was a single false-positive result that occurred among the group of 11 patients with second primary tumors in the lung or elsewhere, thus reflecting the specificity of the ctDNA enrichment panel toward the primary tumor.

Among the 53 patients with NSCLC relapse, the TRACERx team found that some individuals, particularly those with non-adenocarcinoma histology, shed tumor DNA in blood prior to surgery.

This finding proved relevant. ctDNA could be detected at or before relapse in 91% (38/42) of preoperative shedders versus 64% (7/11) of nonshedders.

Notably, the median lead time prior to relapse was 164 days in shedders versus 22 days in nonshedders. continued on page 5

LUNGCANCERNEWS.ORG / JUNE 2020

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MEETING NEWS

cfDNA Analysis Suggests EML4-ALK Variant Does Not Influence Response to Lorlatinib

By Kara Nyberg, PhD

An exploratory analysis of circulating free DNA (cfDNA) shows that lorlatinib confers potent antitumor activity in pretreated patients with ALK-positive NSCLC regardless of EML4-ALK variant type and across a variety of ALK resistance mutations. The duration of response also appears consistent across all ALK fusion subtypes.

“Our patients can [have responses] even after heavy pretreatment with ALK inhibitors and chemotherapy,” remarked lead investigator Todd Bauer, MD, of

Sarah Cannon Cancer Research Institute and Tennessee Oncology. “Tumor tissue data analysis to further support these findings is ongoing,” he added.

One of the benefits of lorlatinib, a third-generation ALK/ROS1 tyrosine kinase inhibitor (TKI), is its ability to maintain activity against most known ALK resistance mutations, including G1202R. Prior research found that EML4-ALK variant type influences the response to ALK TKIs, and Dr. Bauer and colleagues sought to determine whether this holds true for lorlatinib as well. To investigate this issue, the group

Table. ALK Fusion and Mutation Status at Screening

Patients Treated With Prior 2nd-Generation ALK TKIs, n (%) Total ALK Resistance G1202R (156 patients) Mutations Mutation (40 patients) (23 patients) Total ALK fusions

64 (41.0)

28 (70.0)

16 (69.6)

EML4-ALK fusion • Variant 1 • Variant 2 • Variant 3 • Other variants*

27 (17.3) 4 (2.6) 24 (15.4) 5 (3.2)

6 (15.0) 1 (2.5) 18 (45.0) 1 (2.5)

0 (0) 0 (0) 15 (65.2) 0 (0)

Other ALK rearrangements ALK fusion not detected

4 (2.6)

2 (5.0)

1 (4.3)

92 (59.0)

12 (30.0)

7 (30.4)

*Variants 4, 5, 7, and 8.

Abbreviation: TKI, tyrosine kinase inhibitor.

TRACERx Data from page 4

“What these data suggest is that preoperative ctDNA detection status will be a proxy of the potential utility of ctDNA as an MRD biomarker in a clinical setting,” commented Dr. Abbash.

Importantly, tracking MRD using the ctDNA enrichment panel heralded relapse before disease recurrence showed up on standard imaging scans.

For example, 26 patients had one or more surveillance scans showing no evidence of relapse or equivocal changes.

All of these individuals had a preceding blood test positive for MRD, and 24

“Does this assay simply enable us to detect relapse sooner and increase anxiety, or can we actually alter the trajectory and outcome in those who prove positive ahead of radiographic manifestations?”

–Corey Langer, MD, FACP, ILCN Editor

of 26 (92%) went on to develop NSCLC relapse.

“Does this assay simply enable us to detect relapse sooner and increase anxiety, or can we actually alter the trajectory and outcome in those who prove positive ahead of radiographic manifestations?” asked Corey Langer, MD, FACP, of the University of Pennsylvania

performed an exploratory subgroup analysis of cfDNA from 156 patients in the pivotal phase II trial who had previously been treated with at least one second-generation ALK TKI and who received lorlatinib 100 mg QD, the recommended dose. cfDNA analysis using the Guardant 360 platform identified ALK fusions in 41% of the evaluable plasma samples, most commonly EML4-ALK variant 1 or 3 (Table). Forty patients also harbored ALK resistance mutations according to cfDNA analysis, most of whom had either EML4-ALK variant 3 or, to a lesser extent, variant 1. “The presence of an ALK resistance mutation might enrich for EML4-ALK variants 1 and 3,” Dr. Bauer commented.

Notably, among 23 patients with the ALK G1202R resistance mutation, about two-thirds also harbored the EML4-ALK variant 3 fusion, which has been associated with more aggressive disease. “But in the context of lorlatinib’s activity, it doesn’t seem to matter; in fact, this distinction may be moot,” remarked Corey Langer, MD, FACP, of the University of Pennsylvania Abramson Cancer Center, who commented on the study findings.

Indeed, responses occurred across the

Abramson Cancer Center, who critiqued the study findings. “One could posit a trial looking at MRD-positive, radiographically occult relapse or progression, comparing early immunotherapy or chemoimmunotherapy to standard observation,” he suggested.

Indeed, there are clinical trials being planned in advanced NSCLC to put

AACR

COVERAGE EML4-ALK variant subgroups and tended to show similar durability. Objective responses reached 33.3% for patients with variant 1, 75.0% with variant 2, and 45.8% with variant 3 resistance mutations. Median duration of response was 6.9 months for patients harboring variant 1 or 3 resistance mutations and had not yet been reached for patients with variant 2 resistance mutations. For the other 59% of patients in whom no ALK fusions could be detected in plasma, the objective response rate was 39.1% and the median duration of response was 7.1 months.

Some differences may be emerging for progression-free survival outcomes.

However, the evaluable patient numbers are small and longer follow-up is needed.

“It will be interesting to watch this over time to see how these continue to correlate based on the variant subtype,” Dr. Bauer said. ✦ Reference: 1. Bauer TM, Martini JF, Besse B, et al. Impact of the EML4-ALK fusion variant on the efficacy of lorlatinib in patients (pts) with ALK-positive advanced non-small cell lung cancer (NSCLC).

AACR Virtual Meeting; April 27-28, 2020.

Abstract CT025.

the TRACERx technology to the test to examine this very issue. ✦ Reference: 1. Abbosh C, Frankell A, Garnett A, et al.

Phylogenetic tracking and minimal residual disease detection using ctDNA in early-stage NSCLC: A lung TRACERx study. AACR Virtual Meeting; April 27-28, 2020. Abstract CT023.

INDUSTRY AND REGULATORY NEWS Interim Results for CheckMate-743 Positive for Combination Nivolumab/Ipilimumab in Previously Untreated MPM April 20, 2020—Based on a prespecified interim analysis conducted by an independent Data Monitoring Committee, the phase III CheckMate-743 trial found a statistically significant and clinically meaningful improvement in OS for nivolumab plus ipilimumab compared with chemotherapy (pemetrexed and

either cisplatin or carboplatin) for patients with previously untreated unresectable malignant pleural mesothelioma (MPM). Formal data have yet to be released, but the press release stresses that no new safety signals were observed.

Phase III interim results were based on 606 total participants with unresect-

able MPM who were randomly assigned to nivolumab plus ipilimumab (3 mg/kg nivolumab every 2 weeks; 1 mg/kg ipilimumab every 6 weeks) or to chemotherapy.

Secondary endpoints included ORR, disease control rate, PFS, and efficacy measures based on PD-L1 expression level. ✦

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TELEHEALTH SUCCESSES & CHALLENGES

Across specialties, COVID-19 has resulted in increased patient anxiety and decreased in-person appointments. The rapid uptake of telehealth has, for some, widened disparity gaps and been an obstacle in maintaining patient–physician relationships; for others, telehealth has presented an opportunity to provide consistent long-term care to patients in the safety and comfort of their own homes in a manner that is just as personal and perhaps more efficient, depending on the treatment scenario. ILCN will be featuring numerous perspectives from physicians and patients alike in the issues ahead, as well as discussing the “new normal” imposed by the COVID-19 pandemic regarding shifts in provider education, standards of care, and clinical trials. Read ILCN online (lungcancernews.org) for online-only and pre-press content.

Telehealth Is Not a One-Size-Fits-All Approach that many of my patients did not have to drive to Madison to receive care, and the During the past 8 weeks, we have heard ones getting intravenous infusions would how many of our colleagues and cancer decrease their risk of getting COVID-19. centers are switching to teleI believe telehealth has a role health. Two things are in caring for patients with clear during this pancancer: it can increase demic. The first is that access to care in rural cancer centers cannot areas of the country, it wait—most cancer provides an alternative procedures and treatmethod for patients ments are not elective, who may be too weak to and our patients need leave their houses, and it their systemic therapies can facilitate the introducDr. Narjust Duma and bronchoscopies with tion of palliative care.2 Sadly, stent placement to breathe or reality hit. Telehealth is not an continue breathing. Second, the risk of option for all, and it can widen some of infection with SARS-CoV-2 will remain the existing cancer health disparities. high for our patients with lung cancer for Sara is a 69-year-old woman with metthe next several months. These two issues astatic lung cancer who is receiving tarprompted the fast introduction and imple- geted therapy and working full time at her mentation of telehealth in our clinics. chicken farm. When I introduced the idea The term telehealth can be used for sev- of telehealth, Sara was not receptive—she eral types of communication methods with was short on the phone (unusual for her), our patients. The basis of telehealth in the and after 2 minutes of talking about poscurrent environment is to reduce office sible side effects from her medication and visits and face-to-face encounters with our plans for blood work, she quickly ended patients. We, as healthcare workers, are at our conversation. The same happened high risk of being asymptomatic vectors for during our telehealth phone call “everythe virus, thereby exposing our most vul- thing was OK,” even the chickens. During nerable patients. Visits over the phone or our face-to-face visits, I always got stories video constitute the most common forms and complaints about the chickens. I was of telehealth used in thoracic oncology. puzzled; Sara was not acting like herself.

I later learned that she has a very limited The Importance of Touch phone plan, and she was saving phone I previously confessed that “I am a minutes to talk with her grandchildren hugger”; seeing patients, hugging them despite having questions for me. (with their permission), and walking Over the weeks, I sadly learned that them to places after our appointments are Sara’s situation is common for many of some of my favorite parts of my job as my patients; they have limited minutes to an oncologist.1 Human interaction is and talk on the phone, they do not have access will remain essential for oncology care. to the internet, and, for one patient, the Many of us joined this specialty because closest phone on which to receive a call we appreciate human interaction and is at the farm next door. value literally walking with our patients Another common obstacle encounduring their cancer journey. ter while using telehealth is that many Eight weeks ago (or more), everything patients do not feel comfortable with or changed, and now we must show our love have never used a video conference app to our patients by staying away from them. before. Our schedulers are calling our patients and are walking them through Widening—Not Bridging—Gaps how to use our video software, but many Initially, I was excited about the introduc- of my patients are not interested in tion of telehealth to our clinic; I was happy learning despite the best efforts by staff.

By Narjust Duma, MD

Phrases like “Let’s do it over the phone” and “I am too old to learn all of this” were commonly shared with our team.

Our comfort level using this technology should not be taken for granted, and we should not assume that all of our patients want or have the technical knowledge to use our new fancy telehealth tools.

I have completed several telehealth encounters using interpreters; the lack of context and body language made the interpretation, as well as the medical visit, more challenging. It left patients feeling like they were not heard due to existing language barriers.

Additional challenges include reimbursement (phone calls), possible delays in diagnosis and treatment, and the unknown consequences to the patient– physician relationship.

Despite the challenges described above, I believe telehealth is here to stay. I suggest that physicians participate in developing strategies to diminish some of the disparities that may be widened by its use and understand that this set of tools may not work for all of our patients with lung cancer. ✦ About the Author: Dr. Duma is an assistant professor at the University of Wisconsin School of Medicine and Public Health. She is an active IASLC volunteer, serving on both the IASLC Communications Committee and the ILCN Editorial Board. You can follow Dr. Duma on Twitter @NarjustDumaMD. References: 1. Duma N. An oncologist’s perspective of COVID19: “I wish I could hug you.” Oncology Central.

Published March 31, 2020. Accessed May 7, 2020. https://www.oncology-central.com/disease-area/ lung/an-oncologists-perspective-of-covid-19-iwish-i-could-hug-you.

2. Brumley R, Enguidanos S, Jamison P, et al.

Increased satisfaction with care and lower costs: results of a randomized trial of in-home palliative care. J Am Geriatr Soc. 2007;55(7):993-1000.

For tips on how you can optimize and improve patient–physician interactions while using telehealth, watch Dr. Duma’s colleague Dr. Toby Campbell’s Grand Rounds presentation on YouTube. https://bit.ly/3fwOLLg.

Losing the Personal Touch in the Digital World

By Rebecca Matthias

Ms. Matthias is a patient with lung cancer who, along with so many, has transitioned to telehealth. Ms. Matthias lives in Oshkosh, Wisconsin, but she typically travels to Michigan for her preferred provider.

Below are her thoughts on the success of patient–physician communication during the COVID-19 era, including a recent difficult conversation. Ms. Matthias has dualcavity mesothelioma that is active in her right lung. She is currently undergoing radiation therapy and is doing well.

I expected that my first telehealth appointment would have some technical glitches, and it did not disappoint. It took about 5 minutes of my appointment time to be able to hear my doctor because I was unfamiliar with the application being used to Ms. Rebecca Matthias conduct the appointment. I assumed there might be some training or a general tutorial, but nothing was provided. I also expected a nurse or doctor to review medications and current issues as is done in regular appointments, but that also was not done. The doctor did ask how I was doing, but it was not the same as being in the room with him.

I felt detached from the appointment—it did not feel as personal to me as a face-to-face appointment. It’s distract-

I felt detached from the appointment—it did not feel as personal to me as a face-toface appointment. It’s distracting to see a reflection of yourself on the screen. ing to see a reflection of yourself on the screen. Research shows that communication is around 90% to 93% nonverbal, and the truth of this was very evident in the appointment. I felt like I was more rushed, and the conversation was very detached. There was a bit of a lag in transmission that made it even more difficult.

Considering the threat of communicable diseases throughout history, I think there remains good reasons why doctors continued on page 9

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Patient, Provider Safety Paramount During Pandemic: Telehealth Benefits Are Numerous

By Mary Jo Fidler, MD

Healthcare systems in the United States have been slow to adopt telehealth, in part, due to regulatory limitations, patient privacy concerns, and less reimbursement potential.1 However, at the same time, there has been an enormous effort to incorporate electronic health records (EHR) driven by programs such as Meaningful Use by the Centers for Medicare & Medicaid Services (CMS) EHR Incentive Program. Prior to the COVID-19 pandemic, the World Health Organization saw the potential of digital health to extend “the scope, transparency, and accessibility of healthcare” and also saw its potential for accelerating innovation and efficiency.2,3 With access to care limited by the COVID-19 pandemic, regulatory restrictions have been eased in the United States, although several federal and state agencies, as well as regulatory boards are involved including CMS, the Department of Health and Human Services, the Office for Civil Rights (OCR), and the Office of the Inspector General. Particularly important, the OCR will not impose penalties for noncompliance with the

Health Insurance Portability allow for planned scheduled and Accountability Act therapy.

The low use of virtual (HIPAA) provided that telehealth is provided visits prior to COVIDin good faith and that 19 does not seem to be associated with public facing platusability issues nor forms like Facebook patient dissatisfaction.5 Live™ are not used for the communication. 4 In a study of virtual Dr. Mary Jo Fidler Regulations continue to urgent care center visits, evolve and may change by satisfaction surveys showed state. patients were most often very satisSpecific benefits to providers and fied. Within the Rush University Medical patients in a COVID-19 pandemic are Group in Chicago, initial surveys from numerous. These include enabling famthe first 314 responders had 79.6% of ilies to participate while a zero-visitor patients rating the visit a 9 or 10 out of policy is in place, eliminating the need 10, with only 7.6% of patients rating the to touch identifying documents with experience a 6 or lower on the same scale.

In conclusion, with the foundation electronic registration and document uploading, the potential to incorporate that early adaptors of telehealth laid and e-forms for compliance standards such a loosening of restrictions due to the as distress screening, and patient-comCOVID-19 pandemic, the time is right pleted medication reconciliation while for the expansion of telehealth in oncolchecking in electronically. Potential ogy. For the moment, it is an opportuhealth benefits also include screennity to keep our patients and healthcare ing for infectious symptoms prior to providers safe while maintaining prothe patient presenting to the medical vider–patient relationships. In the future, center and reducing potential medical a gradual shift in regulations may allow center exposure for patients who may for expansion of telehealth as a valuehave symptom toxicities that would not based service that may play a bigger

role in models of cancer care delivery. ✦ About the Author: Dr. Fidler is an associate professor in the Department of Internal Medicine at Rush Medical College. She is a member of the IASLC Communications Committee and the ILCN Editorial Group.

References: 1. Flannery D and Jarrin R. Building A Regulatory And Payment Framework Flexible Enough To Withstand Technological Progress. Heath Affairs.

2018;37(12):2052-2059.

2. Jones M, DeRuyter F, Morris J. The Digital Health Revolution and People with Disabilities: Perspective from the United States. Inter J Environmental Research and Public Health.

2020;17(381):1-10.

3. World Health Organization. From Innovation to Implementation: eHealth in the WHO European Region. Published 2016. Accessed May 7, 2020. http://www.euro.who.int/__data/assets/ pdf_file/0012/302331/From-Innovation-toImplementation-eHealth-Report-EU.pdf.

4. U.S. Department of Health and Human Services.

Notification of Enforcement Discretion for Telehealth Remote Communications During the COVID-19 Nationwide Public Health Emergency.

Updated March 30, 2020. Accessed May 7, 2020. https://www.hhs.gov/hipaa/for-professionals/special-topics/emergency-preparedness/notificationenforcement-discretion-telehealth/index.html.

5. Sterling R and LeRouge C. On-Demand Telemedicine as a Disruptive Health Technology: Qualitative Study Exploring Emerging Business Models and Strategies Among Early Adopter Organizations in the United States. J Med Internet Res. 2019;21(11):e14304.

Adapting to the New Virtual Environment: Telehealth Can Be a Patient-First Approach

By Brendon Stiles, MD

Imagine living in a city with more than 180,000 reported cases of COVID-19 and more than 24,000 deaths. Next imagine asking your patients with lung cancer to come into the heart of that city, to a hospital that has cared for hundreds of those patients infected with COVID-19. That is the situation here in New York City and at Weill Cornell’s campus of New YorkPresbyterian Hospital. Given the sobering early reports of higher mortality rates in patients with cancer with COVID-19, it actually became our duty not to put our patients with lung cancer in harm’s way and to ask them to stay away.

To that extent, we pivoted hard towards telehealth. Fortunately, we already had a remarkable system in place through Epic and our electronic medical record.

Weill Cornell Medicine, our Emergency Department in particular, has been a leader in telehealth training over the past few years. We have a Center for Virtual Care that trains physicians and students in “web-side” manner. This includes the basics of how to present yourself online, how to effectively interact with patients, and the skills needed to examine patients remotely. Through training

modules and simulations with standardized patients, trainees can learn how to make and convey treatment-related decisions empathetically while using virtual media. Although I confess that I have never taken any of these courses or modules, having an established focus and process already in place made my transition to telehealth very smooth. In fact, our entire Department of Cardiothoracic Surgery has pivoted to telehealth. For the first week in March, prior to the declaration of the COVID-19 pandemic, only 2.1% of our outpatient clinic visits were virtual. Contrast that with the first week in April, in which 74% of our outpatient encounters were through telehealth. That is a remarkable transition.

Acknowledging Barriers, Maintaining Connections Despite having a good system in place, telehealth can be tricky and takes some getting used to. It may not be for everyone, so I don’t force it on all patients, but rather I give them the option. I understand that virtual interactions may amplify disparities such as those induced by language differences, access to technology, or patient age. At the same time, however, those barriers are often present when I see patients

physically. In addition, the financial and break the tension by commenting on little time strain of getting in and out of a busy visual cues—a picture in the background, hospital should not be underestimated, the pet walking in and out, kids or other particularly for patients who live remotely family members sticking their heads in. or for the elderly. Telehealth takes that Taking a moment to acknowledge burden off of patients and offers those types of things humanthe potential to decrease, izes the visit. Enabled by rather than widen, those tools, I have done things that I would have healthcare disparities.

I have seen that in my thought impossible practice already. The by telehealth such as patients clearly appreexamining a postopciate that aspect. erative incision, telling Of course virtual a patient about a biopsy medicine is different from positive for lung cancer, Dr. Brendon Stiles face-to-face medicine. In and the worst—telling a young never-smoker that her particular, I am a “touch the patient” person, whether it is a firm hand- PET scan looks like she has metastatic lung shake, a hand on the shoulder while lis- cancer. Those were hard to do virtually, but tening to their lungs, or a hug when good the right thing for each of these patients in news is delivered. It is who I am as a doctor, the circumstances. habits that are hard but necessary to break Undoubtedly when we get back to a in the current environment. I worried new normal, there will be times when I how I would connect with patients virtu- will want to see patients face-to-face to ally, new patients in particular. I learned deliver news or to examine them, parquickly that many of the same things are ticularly my new preoperative patients. I important as in the pre-COVID era—eye suspect, however, that many patients will contact, smiles, and asking patients about be comfortable with and prefer telehealth. things other than their illness. The televisits Certainly my patients with lung cancer in particular offer up the potential to see on surveillance can predominantly pivot patients in their own environment and to continued on page 9

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Broad Molecular Testing in Lung Cancer: The Struggle to Translate Recommendations to Clinical Practice

By Kara Nyberg, PhD

2010

Decade in Review

2020

Over the past decade, lung cancer has emerged as a shining example of how precision medicine can dramatically improve patient outcomes. Up to 85% of patients with lung cancer harbor potentially actionable driver mutations, and matching targeted therapy to druggable alterations in the first-line setting prolongs survival two to three times over compared with cytotoxic chemotherapy.1-3 To capitalize on the power of precision medicine for patients, several major medical societies have long recommended routine testing for genomic alterations in driver oncogenes to guide the selection of first-line treatment for patients with NSCLC. Initial guidance in 2013 focused solely on EGFR and ALK mutational analysis for patients with advanced-stage adenocarcinoma,4 but many additional biomarkers have since been added to the diagnostic landscape, both for adenocarcinoma and other disease histologies. Current guidelines now recommend numerous biomarkers for upfront testing at the time of NSCLC diagnosis—EGFR, ALK,

ROS1, BRAF, KRAS, NTRK, MET, RET, and HER2—underscoring the wide breadth of targets and corresponding therapies that can be leveraged for disease management.4-6 The speed at which the field is moving has made it difficult to stay abreast of current testing standards for some oncology facilities, particularly community hospitals that outsource pathology tests or where shortcomings in interdepartmental communication occur. Even when molecular testing involved just a handful of biomarkers, community-based testing lagged behind the benchmarks set in academic practice. An analysis of genomic tests ordered by community oncologists throughout New Jersey and Maryland published in 2017 showed that only 59% of patients underwent EGFR and ALK biomarker testing, and only 8% were tested for all seven mutations recommended by the National Comprehensive Cancer Network guidelines as of 2014.3 The lead author of the study, Martin E. Gutierrez, MD, co-chair of Thoracic Oncology, John Theurer Cancer Center, Hackensack Meridian Health, thinks that testing rates have increased since his study was published, “but there is still a gap that needs to be improved,” he said.

Eric S. Nadler, MD, MPP, who serves as medical director of U.S. Oncology

Health Informatics and Internet Technology at Baylor University Medical Center, confirmed that the rates of genomic biomarker testing are improving but that testing of new markers consistently falls behind that of the familiar ones such as EGFR, ALK, and ROS1.

“Instead of testing [becoming] more streamlined over the past few years, with clear guidelines and guidance, the exposure of testing and manners of testing have made the testing patterns more heterogenous and the practice of ordering specific tests more confusing for the clinical oncologist,” Dr. Nadler said.

“Instead of testing [becoming] more streamlined over the past few years, with clear guidelines and guidance, the exposure of testing and manners of testing have made the testing patterns more heterogenous and the practice of ordering specific tests more confusing for the clinical oncologist.”

–Eric S. Nadler, MD, MPP

Testing deficiencies do not necessarily stem from a lack of awareness. “I think the recognition that testing has to happen is an understood proposition in the community. There are not a lot of patients with adenocarcinoma who

are not getting tested these days,” Dr. Nadler said.

“The problem has to do with logistics more than lack of awareness,” Dr. Gutierrez said. Several retrospective analyses of biomarker testing in realworld clinical practice underscore a variety of clinical and logistical challenges for community-based oncologists.

Common setbacks include insufficient tissue for testing, lack of infrastructure in obtaining and sending biopsy samples for testing, unacceptably long turnaround times for results, and uncertainty regarding reimbursement. As time ticks away in getting all the pieces to fall into place, the pressure to treat patients reaches a tipping point, so sometimes testing is just not done or oncologists resort to chemotherapy before genomic test results are available.

Given the burgeoning number of recommended molecular tests for lung cancer, multigene panel testing using next-generation sequencing (NGS) offers an attractive diagnostic alternative that can keep pace with the dynamics of precision medicine. In a single push, NGS enables identification of all the point mutations, insertions, deletions, copy number alterations, fusion genes, and microsatellite instability information needed to guide the potential use of targeted therapy. NGS can also identify continued on page 12

INDUSTRY AND REGULATORY NEWS Two New Drug Approvals for Mutation-Driven Cancers Change the Therapeutic Landscape of NSCLC May 2020—During the first full week of May, The US Food and Drug Administration (FDA) approved two separate targeted therapies for RET and MET-driven lung cancers, neither of which had pre-existing marker-specific approvals.

Selpercatinib for RET-driven NSCLC Based on the phase I/II LIBRETTO-001 trial, the largest trial of patients with RETdriven cancers, selpercatinib received accelerated approval on May 9, 2020 for patients with metastatic RET fusion-positive NSCLC, agnostic to line of therapy.

LIBRETTO-001 enrolled both treatment-naive (n = 39) and heavily pretreated (n = 105) patients with a RET

fusion-positive NSCLC. The ORR was 85% (95% CI: 70%, 94%) and 64% (95% CI: 54%, 73%), respectively. The median DoR was not reached for treatmentnaive patients, but the minimum DoR was reported as 12 months; median DoR for pretreated patients was 17.5 months (95% CI: 12, not reported).

Prespecified secondary endpoints included central nervous system (CNS) ORR and CNS DoR. Among those patients with NSCLC and measurable brain metastases, 10 of 11 demonstrated intracranial responses. Of these, 100% demonstrated a CNS DoR of > 6 months.

The most frequent serious adverse event was pneumonia. There was a 5% discontinuation rate for patients in LIBRETT0-001, across all cancer types.

Capmatinib for MET-driven NSCLC Just 3 days prior to selpercatinib’s approval, accelerated approval was granted to capmatinib for patients with MET exon 14 skipping mutation-driven NSCLC. A companion diagnostic—the FoundationOne CDx assay— was also approved.

Efficacy was demonstrated in the multicenter, nonrandomized, open-label, multicohort GEOMETRY mono-1 trial, which enrolled 97 patients with metastatic NSCLC with confirmed MET exon 14 skipping mutation. Capmatinib (400 mg, oral, twice daily) was administered until disease progression or unacceptable toxicity. ORR was evaluated by a blinded independent review committee

using Response Evaluation Criteria in Solid Tumors, version 1.1.

ORR for treatment-naive patients (n = 28) was 68% (95% CI; 48%, 84%) with a median response duration of 12.6 months (95% CI: 5.5, 25.3). ORR was 41% (95% CI: 29%, 53%) for patients who had received prior therapy (n = 69) with a median response duration of 9.7 months (95% CI: 5.5, 13.0).

The most common adverse reactions (in ≥ 20% of patients) were peripheral edema, nausea, fatigue, vomiting, dyspnea, and decreased appetite.

Sensitivity to sunlight is possible so patients should be advised to take precautions including covering their skin and using sunscreen. ✦

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Making Mesothelioma Patient Research Happen: The UK Experience

By Liz Darlison, MBE, EN, RN, BSc, MSc; Clare Gardiner, PhD, BSc (hons); Catherine Henshall, MN, RN, MA, PhD; and Angela M. Tod, PhD, MSc, MMedSci, BA (hons), RN

This article has been condensed for print. The full version, including information about the role of a clinical nurse specialist and how they benefit care, as well as more detailed information about each study, can be found at lungcancernews.org.

The United Kingdom has the highest incidence of mesothelioma in the world. More than 2,700 people in the United Kingdom are diagnosed each year.1 Despite epidemiologists predicting that the peak would be reached approximately 5 to 10 years ago,2,3 the incidence continues to rise.

Established almost 16 years ago, Mesothelioma UK is a national charity dedicated to the disease. Mesothelioma UK funds audit and research, and over the last 4 years this has translated into

Losing the Personal Touch

to travel to the appointment and stay over in a hotel, so I had a telephone visit with my provider. This particular visit continue to be one of the few profes- was important because it was to discuss sions that, before COVID-19, have pathology results from a recent biopsy. insisted on seeing people in person. There was concern that my cancer had The idea that seeing a doctor over a returned after 4 years of being stable. device is the same as seeing a doctor My oncologist informed me that the in person has many faults. A doctor cancer had, indeed, returned. It was may need to see things like the color a difficult call to have over the phone of a patient’s skin, because I felt such the clearness of a disconnect with I do concede that there are her eyes, and how my provider. I also situations in which telehealth her heart and lung didn’t have time may be appropriate. However, sound. In addito have a family going to a model of anything tion, patients need member on the call close to 100% telehealth would lead to a significant decline in to feel a personal with me. Therefore, the quality of care. connection with questions went their doctors to unanswered, and share details that might be important. I didn’t really remember the answers A patient may not feel comfortable or to the questions I did ask. The entire like he is in a private space when at call lasted 8 minutes, according to my home, which might lead the patient to phone’s timer. Thankfully, I have his withhold information that might be email address, and he is great about foluncomfortable to discuss. lowing up. He also knows that I have a Because of the pandemic, travel- local doctor who puts “eyes” on me and ing was not advised, as I would need addresses the needs he can. from page 6

EDITOR Corey J. Langer, MD, FACP ASSOCIATE EDITORS Fabrice Barlesi, MD, PhD Caicun Zhou, MD, PhD EDITORIAL GROUP MEMBERS Ross Camidge, MD Edgardo S. Santos Castillero, MD, FACP José Francisco Corona Cruz, MD Marianne Davies, DNP, ACNP, AOCNP Anne-Marie C. Dingemans, MD, PhD Narjust Duma, MD Ivy Elkins Mary Jo Fidler, MD Janet Freeman-Daily, MS, Eng Shirish Gadgeel, MD Deepali Jain, MD Karen Reckamp, MD

Christian Rolfo, MD, PhD, MBA Witold K. Rzyman, MD Beth Sandy, MSN, CRNP Ricardo Sales dos Santos, MD, PhD Joan Schiller, MD Suresh Senan, MD Brendon Stiles, MD Aaron Tan, MD Ricardo Terra, MD, PhD, MPH MANAGING EDITOR AND PUBLISHER Joy Curzio, Curzio Communications COPY EDITORS Alana Williams and Elaine Michl PRODUCTION DIRECTOR Doug Byrnes

spending of almost £1 million ((U.S. $1.2 million). The charity y is the sole funder of the National n nal Mesothelioma Audit and d has released research funds through a number of partner organizations.4 Another major focus for the charity is equitablee access to the best treatment, en nt, care, and support available, lable, able

with a p particular emphasis on clinical tr trials. tria Mesothelioma UK also als so provides support and information for anything in rrelated to mesothelioma including symptoms, support groups, and end-of-life care. This provision is enhanced aand probably dependent on o n the charity’s growing continued on page 12

I do concede that there are situations in which telehealth may be appropriate.

The healthcare system may be overrun, at certain times, if everyone went to the doctor for every cold or cut. If someone needs a simple antibiotic or a referral to another doctor, then a simple video

conference or telephone call may be appropriate. However, going to a model of anything close to 100% telehealth would lead to a significant decline in the quality of care. There are many situations in which seeing a doctor face-toface is essential. ✦

Adapting to the New Virtual Environment

necessity of the COVID-19 pandemic, but it is a change to my practice that I believe is here to stay. Some of that will likely be due to the same necessity of COVID-19. However, I anticipate that some will be due to patient demand for telehealth as we continue to refine it and as we make the experience even better for patients. ✦

from page 7

to virtual visits. These patients navigate New York City to come in for their yearly scan, are stuck in the waiting room with other patients, and generally get to see me for just 5-10 minutes, during which I usually tell them that their scans are ok and that I will see them again next year. We can certainly do that over telehealth, ensure that they are well, and still maintain our personal connection.

In conclusion, my experience with telehealth has been positive. Adopting it into my practice was sped up by the

Purpose and Audience: ILCN: IASLC Lung Cancer News features news about lung cancer research, patient care, tobacco control, and expert commentary from lung cancer leaders. The target audience for this publication is physicians and other specialists involved in the research and treatment of patients with lung cancer and other thoracic oncologic disorders.

Correspondence: Address correspondence to Corey J. Langer, MD, FACP, Editor, c/o curziocommunications@gmail.com.

Change of Address: Postmaster send address changes to ILCN: IASLC Lung Cancer News, c/o IASLC Headquarters, 999 17th Street, Suite 200, Denver, CO, 80202, US.

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Advertising: For information on advertising rates or reprints, contact Kevin Dunn, Cunningham Associates, 201.767.4170, kdunn@cunnasso.com.

All advertising is subject to acceptance by IASLC. IASLC is not responsible for the content of

About the Author: Dr. Stiles is a thoracic surgeon at NewYork-Presbyterian Hospital and an Associate Professor of Cardiothoracic Surgery at Weill Cornell Medicine, New YorkPresbyterian Hospital. He is a member of both the IASLC Communications Committee and the ILCN Editorial Group. Follow Dr. Stiles on Twitter @BrendonStilesMD.

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Disclaimer: The ideas and opinions expressed in ILCN: IASLC Lung Cancer News do not necessarily reflect those of the International Association for the Study of Lung Cancer. The mention of any product, service, or therapy in this publication should not be construed as an endorsement, and the Association accepts no responsibility for any injury or damage to person or persons arising out of or related to any use of material contained in this publication or to any errors or omissions.

IASLC MISSION To embrace the study of the etiology, epidemiology, prevention, diagnosis, treatment, and all other aspects of lung cancer and other thoracic malignancies; to provide education and information about lung cancer and other thoracic malignancies to IASLC members, to the medical community at large, and to the public; to use all available means to eliminate lung cancer and other thoracic malignancies as a health threat for the individual patient and throughout the world.

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E V O LV I N G S TA N D A R D S O F C A R E

TTFields in Unresectable MPM: STELLAR Results in Practice the only adverse event related to the device was skin irritation underneath Tumor-treating fields (TTFields) are a the transducer arrays. Grade 1-2 dernoninvasive, regional treatment based matologic adverse events (dAEs) were on the delivery of low-intensity alternat- observed in 66% of patients; only 5% ing electric fields by transducer arrays had grade 3 skin toxicity, leading to applied to the patient’s skin surround- temporary or permanent interruption ing the tumor.1 TTFields extend survival of the treatment. In the majority of in glioblastoma and are U.S. Food and cases, dAEs were managed with topical Drug Administration (FDA) approved corticosteroids, short treatment breaks, for newly diagnosed and recurrent and a regular shifting of 1-2 cm at each glioblastoma. The STELLAR trial2 was array change. a prospective, phase II, single-arm As with any single-arm phase II pilot study in which patients study, the STELLAR trial has with unresectable maligobvious limitations, sugnant pleural mesogesting that further data t h e l i om a ( M P M ) are needed before there received treatment can be widespread with TTFields, delivimplementation of ered continuously by this therapeutic stratthe NovoTTF-100L egy in clinical practice. system at a frequency However, sample size of 150 kHz, for a planned was relatively large for Dr. Giovanni Luca Ceresoli daily duration of at least 18 a trial in this rare malighours/day. Chemotherapy nancy, and patient baseline with intravenous pemetrexed and plati- characteristics, including ECOG pernum (cisplatin or carboplatin, accord- formance status, were in line with other ing to the investigator’s choice) was recent MPM studies, such as the MAPS4 administered concomitantly at standard and LUME-Meso5 trials. Of note, 26% doses, for up to 6 cycles. Patients whose of patients on the STELLAR trial had disease did not progress after the com- a non-epithelioid tumor, a recognized bined TTFields/chemotherapy regimen negative prognostic factor in MPM. The received maintenance TTFields alone primary outcome measure of the study until unacceptable toxicity, progres- was OS, which, as of 2020, should be sion, or patient refusal intervened. The the standard endpoint for trials in primary endpoint of the trial was OS, advanced MPM, as stated by a recent and the secondary endpoints were PFS, consensus report.6 Endpoints assessed overall response rate (ORR) according to radiographically, such as ORR and PFS, modified RECIST criteria3 per investiga- are challenging in this disease, especially tor’s assessment, 1- and 2-year survival, if a central radiographic review is not and safety. planned. Of note, OS of patients on the Eighty patients were enrolled and STELLAR trial was likely not biased by included in the final analysis. The study post-study treatments (Fig. 2). results showed that TTFields applied to Based on the results of the STELLAR the thorax in combination with peme- trial, the FDA has approved the use of trexed and platinum were an active TTFields with pemetrexed/platinum for and safe option in the frontline treat- the treatment of unresectable locally ment of unresectable MPM. Median advanced or metastatic MPM, under the OS was 18.2 months, with 1-year and Humanitarian Device Exemption path2-year OS of 62% and 42%, respectively way.7 This is the first FDA approval to (Fig.1). Patients with epithelioid sub- be granted for mesothelioma since 2004. type had a median OS of 21.2 months versus 12.1 months for those with non- Areas of Improvement epithelioid tumors. Overall median TTFields act mainly by disrupting the PFS was 7.6 months: 8.3 months in mitotic spindle, but the molecular deterpatients with epithelioid tumors versus minants that affect tumor sensitivity are 6.5 months in patients with non-epi- currently unexplored. The treatment thelioid tumors. A partial response was continues to be studied both preclinically observed in 29 (40%) of 72 evaluable and clinically in MPM as well as in other patients. No increase in systemic tox- solid tumors, such as lung, pancreatic, icity was reported with the addition of ovarian, liver, and gastric cancers. The TTFields to standard chemotherapy; recent availability of an animal model

Fig. 1. STELLAR Trial: Overall Survival

By Giovanni Luca Ceresoli, MD

Median OS was longer in patients with epithelioid histology (21.2 months) than in those with non-epitheliod histology (12.1 months).

Ceresoli et al, Lancet Oncol 2019

Fig. 2. STELLAR Trial: Post-Study Treatments

Patients could have more than one subsequent anticancer therapy. Data were not available in 2 patients.

Ceresoli et al, Lancet Oncol 2019

Fig. 3. Improving Patient Compliance: Skin Care Each set of arrays should be changed at least every 3-4 days.

More frequent array changes may be required in some patients (e.g., during warmer weather or after intense physical activity.)

Careful removal of arrays (taking approximately 60 seconds to remove each array). Excessive force should be avoided. Use mineral (baby) oil on the edge of the arrays during removal.

Shift the arrays of 1-2 cm from the previous position at each change. The skin must be completely dry before applying a new set of arrays.

If there are signs of dermatitis, early treatment with a highpotency topical corticosteroid is recommended (e.g., clobetasol 0.05%, betamethasone 0.05%). When the epidermal barrier is compromised (erosions) or when there are signs of infection, topical antibiotics are recommended.

Lacouture et al, Semin Oncol 2014

using this technology8 could contribute to the identification of biomarkers predictive of benefit. dAEs were the only toxicities directly related to TTFields in the STELLAR trial. Although generally low-grade, easily manageable events, dAEs require the physician’s attention to ensure they do not lead to treatment breaks (Fig. 3).

They can occur as a result of a number of different stimuli, including repetitive mechanical trauma (as in the application and removal of the arrays and in shaving) and inflammation (from the adhesive patch or from the hydrogel covering the ceramic discs).9 A recent metaanalysis10 evaluated the adverse events observed in 192 patients enrolled in four pilot clinical studies addressing different

cancers, where TTFields in combination with chemotherapy were delivered to the torso. Consistent with STELLAR, dAEs occurred in 58% of cases; low-grade dermatitis was reported in 53% and high-grade in 6%. Low-grade pruritus was reported in 9%. There were no other significant TTFields–related AEs. Quality-of-life (QoL) data assessment was not planned in the STELLAR trial.

A secondary analysis of the phase III EF-14 trial in newly diagnosed glioblastoma showed no adverse effect on QoL for the addition of TTFields to standard chemotherapy, except for more itchy skin, an expected consequence from the transducer arrays.11 Similarly, the use of the device is not expected to lead continued on page 11

LUNGCANCERNEWS.ORG / JUNE 2020

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E V O LV I N G S TA N D A R D S O F C A R E

TTFields in Mesothelioma (The STELLAR Trial): More Stars Needed in the Constellation

By Paul Baas, MD, PhD, and Cornedine J. de Gooijer, MD

Recently, a manuscript by Ceresoli et al. was published in The Lancet Oncology.1 The study states that the use of tumortreating fields (TTFields) is a major improvement in the treatment of patients with mesothelioma compared to previous standards.2 Herein, we take a closer look at the study.

Background of TTFields Application

control group receiving chemotherapy alone, statistical significance was not determined.

It is a well-known scientific observation that single-armed studies nearly always tend to overestimate outcomes observed in randomized trials or in the real world. The results of STELLAR suggest similarity with the data obtained from the nintedanib study where the (randomized) phase II single-armed study suggested benefit, but which failed in the phase III setting in mesothelioma.4,5

Previous exp erimental studies have indicated that the use of low- Not Written in the Stars (Yet) The STELLAR trial reported a frequency electric fields may median OS (primary enddisrupt tumor progression through the mitotic point) of 18.2 months spindle during mito(95% CI [12.1, 25.8]). sis. In addition, heat The study looked is produced that may for an OS of 17.6 augment a cytotoxic months, an increase 2 reaction. However, of 5.5 months in cells were only tested median OS compared in vitro, and no clear to the results obtained Dr. Paul Baas explanation is given as to for combination cisplatin why 150 kHz is the optimal and pemetrexed in the regfrequency. istration study in 2003.2 The device has been However, these results should be placed in approved based on the lack of significant the context of recent toxicity and electronic trials in mesothesafety of the apparalioma. 6 The Table shows the objective tus.3 The U.S. Food and Drug Administration, response rate, PFS, and however, did report that OS in previous randomDr. Cornedine J. de Gooijer ized trials in patients with although the results of the STELLAR study are within malignant mesothelioma the range (of reported PFS and OS) and treated with platinum-pemetrexed. show improvement, in the absence of a The confidence intervals observed for

STELLAR Results in Practice from page 10

to QoL deterioration in patients with MPM. At the same time, increased compliance with TTFields therapy was an independent prognostic for survival in the glioblastoma trial.12 Proactive skin care and the availability of a smaller and lighter device may be valuable strategies to improve QoL and compliance to treatment (and ultimately outcomes) in patients with MPM. ✦ About the Author: Dr. Ceresoli is with the Department of Oncology, Cliniche Humanitas Gavazzeni, Bergamo, Italy.

References: 1. Mun EJ, Babiker HM, Weinberg U, et al. Tumor Treating Fields: A fourth modality in cancer treatment. Clin Cancer Res. 2018;24:266-275.

2. Ceresoli GL, Aerts JG, Dziadziuszko R, et al.

Tumor Treating Fields in combination with pemetrexed and cisplatin/carboplatin as first line treatment for unresectable malignant pleural mesothelioma: results of the STELLAR multicenter, single arm, prospective phase 2 trial.

Lancet Oncol. 2019;20:1702-1709.

3. Byrne MJ, Nowak AK. Modified RECIST criteria for assessment of response in malignant pleural mesothelioma. Ann Oncol. 2004;15:257-260.

4. Zalcman G, Mazieres J, Margery J, et al.

Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet.

2016;387(10026):1405-1414.

5. Scagliotti GV, Gaafar R, Nowak AK, et al.

Nintedanib in combination with pemetrexed and cisplatin for chemotherapy-naive patients

Table. Overview of Previous Study Results Study

Number of patients

ORR

mPFS (months; [95% CI])

mOS (months; [95% CI])

Vogelzang2

226

41%

6.1 [5.4-6.7]

12.1 [10.9-14.8]

STELLAR1

80

37%

7.6 [6.7-8.6]

18.2 [12.1-25.8]

MAPS

225

Not reported

7·3 [6·7-8·0]

16·1 [14·0-17·9]

LUME-Meso phase II4

41

44%

5.7 [5.5-7.0]

14.2 [12.3-20.9]

229

43%

7·0 [6·7-7·2]

16·1 [13·7-19·3]

8

5

LUME-Meso phase III

Results are reported from the control arms in the MAPS and both LUME-Meso trials, in which patients received platinum-pemetrexed, and for the cisplatin-pemetrexed arm from the Vogelzang trial.

Abbreviations: mPFS, median progression-free survival; mOS, median overall survival; ORR, objective response rate.

TTFields in combination with standard chemotherapy in the STELLAR trial overlap with historical data. Although the authors attributed the lack of benefit for angioinhibitory strategies in the MAPS and LUME-Meso trials to a patient population with a worse prognosis (more patients with sarcomatoid mesothelioma), other prognostic factors (like platelet count and lactate dehydrogenase) were not reported. This underscores the need for randomized studies to reveal the true added benefit of TTFields in mesothelioma.

The monthly costs of TTFields ($21,000 in 2016) and the effect on quality of life need to be justified based on phase III data. TTFields were used continuously during the four cycles of platinum-pemetrexed therapy and as maintenance therapy until progression. Patients received a median of eight cycles of TTFields, hence a median 5.5 months of continual use of this device. The effect on quality of life for patients and relatives should not be underestimated.7 The TTFields device, applied to the thorax, is recommended to be used for 18 hours per day (also at

night). In 66% of patients, a local reaction to the skin at the site of the medical device was observed.1 Based on the results of this study, we conclude that the TTFields approach may hold some promise, but there is a clear lack of prospective phase III evidence. A randomized study is of paramount importance, and more insight into its working mechanisms is needed.

Differences in pathology and performance status of the patients enrolled on this study compared to populations on other trials and historic controls can account for potential spread in outcome.

Finally, we need to focus on translational research factors to support a role for this device. ✦

with advanced malignant pleural mesothelioma (LUME-Meso): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet Respir Med. 2019;7(7):569-580.

6. Tsao AS, Lindwasser OV, Adjei AA, et al.

Current and future management of malignant mesothelioma: a consensus report from the National Cancer Institute Thoracic Malignancy Steering Committee, International Association for the Study of Lung Cancer, and Mesothelioma Applied Research Foundation. J Thorac Oncol.

2018;13:1655-1667.

7. NovoTTFTM - 100L System - H180002. U.S. Food and Drug Administration. https://www.fda.gov/ medical-devices/recently-approved-devices/ novottftm-100l-system-h180002. Published May 28, 2019. Accessed January 12, 2020.

8. Voloshin T, Kaynan N, Davidi S, et al. TumorTreating Fields (TTFields) induce immunogenic cell death resulting in enhanced antitumor efficacy when combined with anti-PD-1 therapy.

Cancer Immunol Immunother. 2020 Mar 6.

[Epub ahead of print].

9. Lacouture ME, Davis ME, Elzinga G, et al.

Characterization and management of dermatologic adverse events with the NovoTTF-100A System, a novel anti-mitotic electric field device for the treatment of recurrent glioblastoma.

Semin Oncol. 2014;41(Suppl 4):S1-S14.

10. Ceresoli GL, Vergote I, Rivera F, Pless M. Safety of Tumor Treating Fields delivery to the torso: pooled analysis from TTFields clinical trials (Abstract 8215). Proceedings of the 2019 Annual Meeting of the American Association for Cancer Research. 2019;79(13 Suppl.).

11. Taphoorn MJB, Dirven L, Kanner AA, et al.

Influence of treatment with tumor-treating fields on health-related quality of life of patients with newly diagnosed glioblastoma: A secondary analysis of a randomized clinical trial. JAMA Oncol.

2018;4(4):495-504.

12. Toms SA, Kim CY, Nicholas G, Ram Z. Increased compliance with tumor treating fields therapy is prognostic for improved survival in the treatment of glioblastoma: a subgroup analysis of the EF-14 phase III trial. J Neuro Oncol. 2019;141(2):467-473.

About the Authors: Dr. Baas is chief of Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.

Dr. de Gooijer is with the Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.

Please note that the full reference list for this article appears online at lungcancernews.org.

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IASLC LUNG CANCER NEWS / JUNE 2020

Mesothelioma Patient Research from page 9

team of mesothelioma clinical nurse specialists (CNSs).

Mesothelioma UK is committed to ensuring that those diagnosed with mesothelioma have support opportunities equal to that of all patients with cancer through National Health Service (NHS) access to a nurse specialist who is an expert in all aspects of mesothelioma.

Currently, the charity provides funding for 25 mesothelioma CNSs based in NHS hospitals across the United Kingdom.

Creating a national expert team of specialist nurses has enabled nationwide insight and experience to be generated and collated regarding mesothelioma.

Linking with academic colleagues and institutions, the following studies have been developed with and fully supported by the Mesothelioma UK CNS team.

Mesothelioma and Radical Surgery (MARS STUDY 2): Patient Experience Arm of a Feasibility Trial 1 MARS 25,6 aimed to evaluate the benefits of surgery by comparing chemotherapy and surgery against

Broad Molecular Testing from page 8

genomic alterations that open the door to clinical trials of investigational therapies.

“NGS should absolutely be the standard of care at this point, especially now that payers are starting to cover it,” said Nathan A. Pennell, MD, PhD, of the Taussig Cancer Institute, Cleveland Clinic Foundation. Three tissue-based NGS tests have been approved by the U.S. Food and Drug Administration for patients with lung cancer: FoundationOne CDx, the Oncomine Dx Target Test, and the MSKIMPACT assay. Moreover, in 2017, the U.S. Centers for Medicare and Medicaid Services (CMS) approved coverage of NGS testing under the Parallel Review Program, and private payers have started to follow suit.

“There are too many biomarkers to do individual gene tests anymore; you just can’t get them all done. And it costs a lot more to do multiple tests and bill for each individually than it does to do one NGS test,” Dr. Pennell said. Dr. Pennell and his colleagues recently devised a mathematical model that showed that upfront tissue-based NGS testing was both faster—with a 2-week turnaround time—and less costly than testing sequentially for alterations in EGFR, ALK, ROS1, BRAF, MET, HER2, RET,

chemotherapy alone. Semi-structured telephone interviews were conducted post-randomization, post-surgery (surgery arm), and at 6 and 12 months.

ing the incidence of mesothelioma confirmation review among UK military personnel and a literature review explorand veterans, although it is suspected that this group may ing the existing encounter particular chalresearch about Receiving a Diagnosis of lenges, including securing the psychologMesothelioma (RADIO timely diagnosis, accessing ical effects of STUDY Meso): Improving the care and support, and obtainmesothelioma 2 Patient Experience ing financial help. MiMES aims on patients and Dr. Clare Gardiner RADIO Meso5,7 aimed to address these issues. caregivers. to understand the experiData collection is Once ethics clearance has been obtained, ence of communicating a now complete, analysis is diagnosis of malignant ongoing, and findings approximately 10 participants are pleural mesothelioma are being tested among expected to be interviewed, beginning (MPM) from the perstakeholders. We are in the spring of 2020. Expected date of spective of patients, developing some edu- completion is summer 2022. family caregivers, and cational materials for Mesothelioma Patients’ health professionals. health professionals and other support staff Experiences of Follow-Up Key findings include the importance of providthat will help inform the Across Three NHS Trusts STUDY Ms. Liz Darlison ing the diagnosis as an ongoprovision of services to A qualitative study using 5 ing process and the need to individuals with an armed documentary analysis, provide continuity and consistency. forces background who have been diag- interviews, and consultation meetings nosed with mesothelioma. The expected with stakeholders. The recommendations Military Mesothelioma date of completion is June 2020. developed suggest that all patients with Experience Study mesothelioma have access to a specialist MiMES PhD Studentship mesothelioma team within a streamlined STUDY (MiMES): Understanding the Impact of As part of the MiMES mesothelioma care pathway and that 3 Mesothelioma for STUDY project, Mesothelioma UK patients are equipped with the necesMilitary Personnel and Veterans has funded a PhD student, sary information to guide their decision 4 There is currently no evidence reportwho has completed her continued on page 13

and NTRK1 using single-gene tests or testing simultaneously for alterations in EGFR, ALK, ROS1, and BRAF using hotspot panels followed by single-gene tests for the remaining biomarkers.7 Although NGS offers an obvious solution for hospitals that lack testing capabilities, NGS uptake in community settings remains anemic due to many of the same clinical and logistical problems that plague single-gene tests. Obtaining adequate tissue still tops the list of challenges.

“Frequently in the community, tissue is obtained by bronchoscopy, so bronchoalveolar lavage or fine needle aspira-

one must take negative liquid biopsy results with a grain of salt due to variable amounts of tumor DNA shed into circulation and lower sensitivity levels compared with tissue-based testing, positive results are clinically actionable. Thus, plasma NGS offers a means to enhance testing rates and improve widespread delivery of molecularly guided therapy.

Aside from leveraging tissue or plasma NGS for newly diagnosed patients with lung cancer, Dr. Pennell believes that one of the simplest ways to improve broad molecular testing within institutions is to promote internal communication.

Although NGS offers an obvious solution for hospitals that lack testing capabilities, NGS uptake in community settings remains anemic due to many of the same clinical and logistical problems that plague single-gene tests. Obtaining adequate tissue still tops the list of challenges. tion cytology is all that is available,” Dr. Gutierrez said. “The lack of tissue when you want to do tissue-based NGS can be a nightmare,” which has prompted Dr. Gutierrez to order plasma-based cell-free circulating tumor DNA NGS testing up front in appropriate settings—for example, if a patient is referred to him with only a fine needle aspiration specimen.

Accumulating data support the use of plasma NGS as a worthy tool for genomic biomarker testing, especially in situations where tissue is scarce.8,9 Although

“Have a conversation with all the stakeholders—the pathologists, the interventional radiologists, the pulmonologists, the surgeons—to make sure everyone knows the importance of molecular testing and ensures that it’s a priority.”

Dr. Pennell hopes that these conversations will boost lung cancer to the same level as breast cancer in terms of molecular testing. “You’d be shocked if you walked into any oncology office in America to see a woman with breast cancer who did not have a pathology

report listing estrogen-receptor, progesterone-receptor, and HER2 FISH status along with the diagnosis and grade,” he explained. “Molecular testing has become a standard component of breast cancer care. And yet when we talk about lung cancer, molecular testing doesn’t get that same gut-level understanding of how important it is. It almost seems more optional, and it’s not,” Dr. Pennell said. ✦ Please note that the full reference list for this article appears online at lungcancernews.org.

References: 1. Jordan EJ, Kim HR, Arcila ME, et al. Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies. Cancer Discov. 2017;7(6):596-609.

2. Nadler E, Espirito JL, Pavilack M, Boyd M, Vergara-Silva A, Fernandes A. Treatment Patterns and Clinical Outcomes Among Metastatic NonSmall-Cell Lung Cancer Patients Treated in the Community Practice Setting. Clin Lung Cancer.

2018;19(4):360-370.

3. Gutierrez ME, Choi K, Lanman RG, et al.

Genomic profiling of advanced non-small cell lung cancer in community settings: gaps and opportunities. Clin Lung Cancer. 2017;18(6):651659.

4. Lindeman NI, Cagle PT, Aisner DL, et al.

Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: guideline from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. J Thorac Oncol. 2018;13(3):323-358.

LUNGCANCERNEWS.ORG / JUNE 2020

Mesothelioma Patient Research

patients with palliafrom page 12 tive care needs and their families. making with regard to standard treatWe hope this ment pathways. research will The findings are being written up contribute to for publication in a peer-reviewed acabetter underdemic journal. We are working with standing of the Mesothelioma UK to disseminate our care and support Prof. Angela M. Tod recommendations with the aim of using individuals diagthese to influence policy and practice to nosed with mesotheimprove the quality of care received by Mesothelioma and lioma need toward the end patients with mesothelioma. of life, and will establish the important Asbestos Guidelines STUDY Study (MAGS) role of Mesothelioma UK CNSs in meet9 Exploring Clinical MAGS aims to explore the ing these needs.

Decision Making in experiences of presentaAn experienced research associate STUDY Mesothelioma Treatment tion, diagnosis, treatment, and care for has recently been appointed to manage 6 Pathways Across Three healthcare workers with mesothelioma. the study and will begin her role in NHS Trusts: A MixedThe study will develop a critical account April 2020. Expected date of compleMethods Study of that experience, which will aid in the tion is June 2021. development of recommendations to Although a mixed-methods study using database analysis, interincrease awareness about the In Summary views, and consultation dangers of asbestos among In just a few years, the collaboration meetings with stakehealthcare workers. between an expert team of nurses, holders was expected Malignant mesoa charity committed to patients, the to commence in thelioma (MM) is an NHS, and successful health academics March 2020, it is aggressive, rare cancer has resulted in an excellent, clinically now on hold due to caused by exposure relevant portfolio of research. The colCOVID-19 restricto and inhalation of laboration supports the identification of tions. asbestos. Incidence is relevant studies, the securing of research NHS Health Research higher in certain occugrants, and the dissemination of findDr. Catherine Henshall pational groups, although Authority approvals for this ings. Tools and resources have been study have been obtained. healthcare is not considered developed on the basis of findings from a high-risk industry for MM. Despite the research, ensuring timely and maxiLiving Well With this, many healthcare workers work in mum impact.

Malignant Pleural old buildings in which asbestos is likely STUDY Mesothelioma (MPM): to be present. There is a concern that The hub-and-spoke national 7 Improving the Patient cases of MM due to such exposure could approach to specialist nursing, and Family Caregiver increase over time. Raised awareness appropriate funds or grants, and and action taken by individual healthExperience: A Qualitative Study a close working relationship with This study seeks to identify core themes care workers and employers could help committed health academics are and recommendations for “living well” avoid this. all equally essential. for individuals with MPM and their A rapid review of published and family members and caregivers and to unpublished research examining the identify recommendations to help them experience of healthcare workers This approach is replicable in other achieve meaningful and fulfilling lives. who have developed mesothelioma is countries. The hub-and-spoke national Individual interviews are completed complete. A Freedom of Information approach to specialist nursing, appropriand transcribed, and analysis of tran- request has been submitted to identify ate funds or grants, and a close workscription is currently being conducted. how many cases have been submitted ing relationship with committed health Expected date of completion is August against the NHS for mesotheliomaacademics are all equally essential.

2020. related compensation. This is partially Opportunities to forge global partnercomplete and reveals higher levels of ships would be welcome. ✦ Gendered Experience mesothelioma in the population of healthcare workers than shown by the About the Authors: Ms. Darlison is head of of Mesothelioma Study STUDY (GEMS) Office for National Statistics mesotheServices, Mesothelioma UK, and Consultant 8 GEMS aims to explore the lioma mortality figures.

Nurse, University Hospitals Leicester, United Kingdom. Dr. Gardiner is senior research experiences of men and women with mesothelioma, their family Understanding the Role fellow, Health Sciences School, The University of Mesothelioma UK caregivers, and the various staff they meet of Sheffield, United Kingdom. Dr. Henshall is STUDY CNSs in Meeting the and to understand the reason for any difNational Institute for Health Research 70@70 10 ferences that are identified between the Palliative Care Needs of senior nurse research leader, and senior nursing research fellow, Oxford Brookes Patients and Families: experiences of men and women. Our goal is to establish with participants how A Mixed-Methods Study University, and head of Research Delivery, services should best be delivered to be The aim of this study is to explore the Oxford Health NHS Foundation Trust, United Kingdom. Prof. Tod is professor of accessible and acceptable to both men palliative care needs of patients with and women. mesothelioma and to assess the diverse Older People and Care, Division of Nursing Secondary analysis of data from ways in which Mesothelioma UK CNSs and Midwifery, The University of Sheffield, an asbestos support group has been are helping support and empower United Kingdom. conducted to examine similarities and differences by gender.

Consultations on the findings are currently being conducted with mesothelioma nurse specialists, asbestos support group forums, solicitors, and patient groups.

Expected date of completion is August 2020.

13

References: 1. Cancer Research UK. Mesothelioma statistics.

Accessed March 5, 2020. https://www. cancerresearchuk.org/health-professional/cancerstatistics/statistics-by-cancer-type/mesothelioma.

2. Peto J, Matthews FE, Hodgson JT, Jones JR. Continuing increase in mesothelioma mortality in Britain. Lancet. 1995;345(8949):535-539.

3. Hodgson JT, McElvenny DM, Darnton AJ, Price MJ, Pete J. The expected burden of mesothelioma mortality in Great Britain from 2002-2050. Br J Cancer. 2005;92(3):587-593.

4. Royal College of Physicians. National Mesothelioma Audit. Accessed April 5, 2020. https://www.rcplondon.ac.uk/projects/nationalmesothelioma-audit.

5. The University of Sheffield. Mesothelioma Patient Experience Research Group. Accessed April 5, 2020. https://www.sheffield.ac.uk/health-sciences/ our-research/nursing-themes/enhancing-lives/ mesothelioma-patient-experience-researchgroup.

6. Warnock C, Lord K, Taylor B, Tod A. Patient experiences of participation in a radical thoracic surgical trial: findings from the Mesothelioma and Radical Surgery Trial 2 (MARS 2). Trials.

2019;20:598.

7. Taylor B, Warnock C, Tod AM. Communication of a mesothelioma diagnosis: developing recommendations to improve the patient experience.

BMJ Open Respir Res. 2019;6:e000413.

INDUSTRY AND REGULATORY NEWS FDA Approves Durvalumab for Extensive-Stage SCLC March 27, 2020—The U.S. Food and Drug Administration approved durvalumab in combination with etoposide and either carboplatin or cisplatin for the first-line treatment of patients with extensive-stage SCLC. The approval was based on the randomized, multicenter, openlabel, active-controlled CASPIAN trial, which compared durvalumab plus chemotherapy vs chemotherapy alone for previously untreated patients with extensive-stage SCLC. In CASPIAN, median OS was 13.0 months (95% CI: 11.5, 14.8) for the combination compared with 10.3 months (95% CI: 9.3, 11.2) for chemotherapy alone (HR 0.73; 95% CI: 0.59, 0.91; p = 0.0047). Median PFS was 5.1 months (95% CI: 4.7, 6.2) and 5.4 months (95% CI: 4.8, 6.2), respectively. ORR was 68% (95% CI: 62, 73) and 58% (95% CI: 52, 63), respectively.

With this approval, durvalumab joins atezolizumab in combination with standard platinum and etoposide as options for front-line treatment in the management of chemotherapy-naive extensivestage SCLC. ✦

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IASLC LUNG CANCER NEWS / JUNE 2020

G L O B A L I N I T I AT I V E S

Lung Cancer in the Brazilian Health System: Screening, Drug Approvals, Barriers to Care, and Success Stories According to a large Fig. Geographic Representation of Lung Cancer Adjusted Incidence Rates Per A) 100,000 Men and 25 cancer registry database B) 100,000 Women, Estimated for 2020 in Brazil study, which included a The reality of lung cancer in Brazil is as total of 35,018 patients alarming as it is in the rest of the world. diagnosed with NSCLC, However, problems related to the diagno- and data from 258 hospisis and treatment of lung cancer in Brazil tals in 25 states of Brazil are aggravated by intrinsic characteristics and the Federal District of the national health system. The lack (Brasília) between 2000 of access to healthcare in certain regions and 2011, a progresinterferes with the analysis of lung cancer sive increase occurred in incidence and mortality in the country. the percentage of cases Each year, approximately 30,000 new of advanced stages of cases of lung cancer are diagnosed in NSCLC. 8 Efforts have Brazil.1,2 The southern and southeastern been made to promote regions have higher lung cancer preva- expansion of cancer care lence rates (between 20 and 55 cases per to the Brazilian popu100,000 inhabitants) than the northern lation in the Brazilian and northeastern states (less than 10 Public Health System (SUS). The in different regions of the country have therapy equipment. However, it is notecases per 100,000 inhabitants; Brazilian Ministry of Health started isolated screening programs. At worthy that the availability of appliances Fig.).3 A possible explanaimplemented in 2000 the the moment the data from these pro- and especially disposable equipment is tion for this fact lies in “Expande” Project, with grams are being consolidated for a more almost exclusive to the private healtha broader coverage of the coordination of detailed discussion, in partnership with care system.18 By 2020, fewer than five cancer services in the the National Cancer the “Propulmão” Program, an initiative public hospitals could be cited as one of South and Southeast Institute of Brazil. of medical practitioners and healthcare the state-of-the-art lung cancer care proregions of Brazil, The principal goals professionals whose mission is to pre- viders nationwide. which have more than of this project were to vent lung cancer through education, Brazil is a country of continentwice as many speexpand access to cancer awareness, and discussion on lung tal dimensions which, despite having cialized centers when treatment in the country care.14 among the 10 largest economies in the Dr. Ricardo Sales dos Santos compared to the other and also to reduce regional One of the basic and important barriers world, still faces structural problems in mentioned regions. The inequalities.9 to lung cancer screening is the number sanitation, outbreaks of infectious dislow supply of cancer serof CT scanners in the public system, eases, and epidemics of communicable vices yields fewer diagScreening which is responsible for the healthcare diseases. In addition, violence accounts noses and possibly Since the results of of approximately 70% of the Brazilian for thousands of deaths each year.19 In many deaths without the National Lung population. The private system has six this context, discussion about the treata defined cause; this Screening Trial were times more CT scanners, with numbers ment of lung cancer in advanced stages, may be related to published in 2011,10 similar to those found in high-income with appropriate access to molecular tests the diagnosis of lung efforts have been countries.15 and coverage of the costs of new drugs cancer or other types made to implement in precision oncology, confronts several of cancer. screening programs in Overcoming Obstacles practical and theoretical obstacles for Dr. Juliana Franceschini Fortunately, there has Brazil. Between 2013 and Brazil has just over 700 thoracic sur- wider availability to the population.20 In been a major drop-off in 2016, results of the fi rst geons and approximately 600 radiation many cases, patients need to go to court smoking rates in Brazil since the 1980s, Brazilian national screening study oncologists, for an estimated population to access high-cost medications in the 11,12 of more than 200 million. (In contrast to public and private system. Access is furreducing the number of smokers by more (BRELT1) were published.

BRELT1 than 50%, thanks to adherence to public validated low-dose CT imaging as a the United States, only general thoracic ther affected by the rapid advancement policies on cigarette control with tax screening method in our region, which surgeons and not cardiothoracic sur- and specificities of the new technologies, increases, a smoking ban in public places, has a high rate of granulomatous disgeons are included in this specialty in which are often inaccessible either due and limitations on cigarette advertising.4-6 ease. We noticed that this rate did not Brazil.) Despite the reasonable number to the clinical condition of the patients, increase the number of biopsies nor did of professionals, there is a higher con- many of whom are too ill to benefit, or centration of these individual in large due to competing priorities in the case Diagnosis it affect the prevalence of lung cancer Unfortunately, most cases of lung cancer compared to other studies published in centers, in cities with more than one mil- of public health managers, who are comin Brazil are diagnosed at an advanced the northern hemisphere: biopsies were lion inhabitants (15 cities in the country, pelled to cover high costs without the three of them in the state of São Paulo).16 certainty of therapeutic efficacy. stage; fewer than 10% of cases are diag- performed in approximately 3% of the 7 nosed at an early stage (stages I and II).

790 study participants, and diagnosis Furthermore, there is a shortage of radioHowever, headway is being made.

Symptomatic patients have great difficulty of early stage lung cancer occurred in therapy devices, with fewer than 250 There are promising initiatives involving in securing a diagnosis in both the public 1.5% of participants. Despite these data, units nationwide, and this greatly slows research groups allied with the pharmaand private healthcare systems. Various to date, there are no national public access to radiotherapy treatment.17 ceutical industry to provide large-scale analyses of patients diagnosed with lung policies on the subject. Nor are there Since 2010, new technologies for the molecular testing for patients diagnosed cancer show that most require multiple definitive statements from specialized diagnosis and treatment of lung cancer with lung cancer. Some pharmaceutical medical appointments and face difficul- national medical entities supporting have been established in different states, companies offer molecular testing with ties in screening or work-up, delaying screening as it should be supported.13 In such as endobronchial ultrasound, free access to doctors and no charge for diagnosis by many weeks or months.4 this scenario, some medical institutions robotic surgery systems, and ablative continued on page 15

By Ricardo Sales dos Santos, MD, PhD, and Juliana Franceschini, PhD

LUNGCANCERNEWS.ORG / JUNE 2020

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Names and News David L eDuc has been named Associate Director, Oncology Patient Affairs at AstraZeneca. In this role, Mr. LeDuc will be responsible for building and strengthening relationships with key stakeholders and advocates and incorporating the patient voice in all aspects of the company’s work. Mr. LeDuc came to AstraZeneca from the Go2 Foundation for Lung Cancer, where he was Executive Director and then Chief Growth Officer.

Shirish Gadgeel, MD, is now the Chief of Division of Hematolog y and Oncolog y and Associate Director of Patient Experience and

Lung Cancer in Brazil from page 14

patients21-24; such partnerships should allow information on the occurrence of mutations and molecular biomarkers in our population to be reported, with better delineation of public policy in the acquisition of medicines.

In our opinion, one of the greatest challenges of the Brazilian health system is the need to integrate the activities of the private system with the public system, generating demand and access in an organized and structured way to various technologies already available in some regions. New value-based compensation models need to be quickly tested and made viable, at the risk of further disruption of the provision of medical services. ✦ About the Authors: Dr. Sales dos Santos is the head of Respiratory Medicine at Hospital Cárdio Pulmonar, Salvador/Bahia, Brazil. He works as staff thoracic surgeon at Hospital Israelita Albert Einstein, São Paulo, and CLION, Einstein’s Oncology Network, Salvador/Bahia, Brazil. He contributes as member of IASLC´s Screening & Early Detection Committee, ProAr Foundation, and Propulmão Program.

Dr. Franceschini is a physical therapist and research coordinator at Propulmão Program, project manager at ProAr Foundation, and a postdoctoral researcher in the Respiratory Division, Universidade Federal de São Paulo/ UNIFESP, Brazil.

Clinical Care at Henry Ford Cancer Institute/Henry Ford Hospital, Detroit, Michigan. He is also a Professor at Wayne State University, where he previously served as leader of the Thoracic Oncology Multidisciplinary Team and Associate Professor of Internal Medicine. He also served as the coleader of the Molecular Therapeutics Research Program of the Core Cancer Center Grant of Karmanos Cancer Institute in Detroit. Dr Gadgeel has also been a Principal Investigator (PI) of a Southwest Oncology Group trial, S0528. Dr. Gadgeel is an extremely active member of IASLC. He is a member of the editorial board for the Journal of Thoracic Oncology, the editorial group for ILCN, and of the IASLC Communications Committee and the ILCN Editorial Group.

Gideon Blumenthal, MD, has transitioned from Deputy Director of the Oncology Center of Excellence

Visit JTO.org to read a more extensive article published in February 2020 about lung cancer prevention, diagnosis, and treatment in Brazil.

Regional perspectives also are available at JTO.org for: • China, • Italy, • Canada, • Saudi Arabia, • and 14 other countries.

References: 1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin.

2018;68(6):394-424.

2. Ferlay J, Colombet M, Soerjomataram I, et al.

Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019;144(8):1941-1953.

3. INCA. Estimativa 2018: incidência de câncer no Brasil. Rio de Janeiro: INCA; 2017:128.

4. de Sa VK, Coelho JC, Capelozzi VL, de Azevedo SJ. Lung cancer in Brazil: epidemiology and treatment challenges. Lung Cancer (Auckl).

2016;7:141-148.

5. Monteiro CA, Cavalcante TM, Moura EC, Claro RM, Szwarcwald CL. Population-based evidence of a strong decline in the prevalence of smokers in Brazil (1989-2003). Bull World Health Organ.

2007;85(7):527-534.

6. Ministério da Saúde. Vigitel Brazil 2018: surveillance of risk and protective factors for chronic diseases by telephone survey: estimates of frequency and sociodemographic distribution of risk and protective factors for chronic diseases in the capitals of the 26 Brazilian states and the Federal District in 2018. Brasília: Ministério da Saúde; 2019:132.

7. Araujo LH, Baldotto C, Castro G, Jr., et al. Lung cancer in Brazil. J Bras Pneumol. 2018;44(1):55-64.

(OCE) at the U.S. Food and Drug Administration (FDA) to Vice President of Global Regulatory Affairs for Oncology at Merck. Dr. Blumenthal was with the FDA for more than a decade, after more than 12 years of service at the National Cancer Institute.

Paul G. Kluetz, MD, has been named the FDA’s new Deputy Director of the OCE. During his 10 years with the FDA, Dr. Kluetz founded the OCE’s PatientFocused Drug Development program.

The IASLC looks forward to our continued collaboration and partnership with the FDA with regard to lung cancer therapies, diagnostics, and policies,

8. Costa G, Thuler LC, Ferreira CG. Epidemiological changes in the histological subtypes of 35,018 non-small-cell lung cancer cases in Brazil. Lung Cancer. 2016;97:66-72.

9. INCA. Expansão da Assistência Oncológica (Projeto EXPANDE) Rio de Janeiro: INCA. https://www.inca.gov.br/acesso-a-informacao/ acoes-e-programas/projeto-expande. Published 2018 [updated July 17, 2018]. Accessed January 9, 2020.

10. Kramer BS, Berg CD, Aberle DR, Prorok PC. Lung cancer screening with low-dose helical CT: results from the National Lung Screening Trial (NLST). J Med Screen. 2011;18(3):109-11.

11. Santos RS, Franceschini JP, Chate RC, et al. Do Current Lung Cancer Screening Guidelines Apply for Populations with High Prevalence of Granulomatous Disease? Results from the First Brazilian Lung Cancer Screening Trial (BRELT1).

Ann Thorac Surg. 2016;101(2):481-488.

12. Santos RS, Franceschini JP, Kay FU, et al. Lowdose ct screening for lung cancer in brazil: A study protocol | Rastreamento de cancer de pulmão por meio de TC de baixa dosagem no Brasil: Protocolo de pesquisa. J Bras Pneumol.

2014;40(2):196-199.

13. Mathias C, Prado GF, Mascarenhas E, et al. Lung Cancer in Brazil. J Thorac Oncol. 2020;15(2): 170-175.

14. Propulmão Program. http://www.propulmao. com.br/. Accessed January 9, 2020.

15. FIOCRUZ. A saúde no Brasil em 2030 prospecção estratégica do sistema de saúde brasileiro: estrutura do financiamento e do gasto setorial. 22 ed. Rio de Janeiro: Fiocruz/Ipea/ Ministério da Saúde/Secretaria de Assuntos Estratégicos da Presidência da República; 2013:168.

16. Tedde ML, Petrere Jr. O, Pinto Filho DR, et al.

General thoracic surgery workforce: training, migration and practice profile in Brazil. Eur J Cardiothorac Surg. 2015;47(1):e19-24.

17. Ministério da Saúde. Censo Radioterapia.

Brasilia; 2019:10.

18. Interfarma. Câncer no Brasil - A jornada do paciente no sistema de saúde e seus impactos sociais e financeiros. Associação da Indústria Farmacêutica de Pesquisa (Interfarma); 2019:88.

19. Reis C, Barbosa L, Pimentel VP. O desafio do envelhecimento populacional na perspectiva

such as major pathologic response and smoking cessation.

In addition to her roles of Associate Director for Clinical Research at Cedars-Sinai Cancer and Medical Oncology Director of Women’s Guild Lung Institute in the Department of Medicine at Cedars-Sinai Cancer, Karen L. Reckamp, MD, MS, has been named the Director of the Division of Medical Oncology there. Most recently, Dr. Reckamp served as Co-Director of the Lung Cancer and Thoracic Oncology Programs and Medical Director of the Clinical Research Operations and Clinical Trials Office at City of Hope.

Dr. Reckamp is an active IASLC volunteer, serving as a member of both the Communications Committee and the ILCN Editorial Group. ✦

sistêmica da saúde. BNDES Setorial. 2016;44:37.

20. Kaliks RA, Matos TF, Silva VA, Barros LHC. Differences in systemic cancer treatment in Brazil: my Public Health System is different from your Public Health System. Braz J Oncol.

2017;13(44):12.

21. Bristol-Myers Squibb. IODetect. https://www. iodetect.com.br. Accessed January 9, 2020.

22. MSD. PD-Point – Programa de Biomarcador MSD. https://www.pdpoint.com.br. Accessed January 9, 2020.

23. Pfizer. PfizerAlvo. http://alkalvo.com.br. Accessed January 9, 2020.

24. AstraZeneca. ID. http://www.programaid.com.br.

Accessed January 9, 2020.

25. INCA. Neoplasia maligna da traqueia, dos brônquios e dos pulmões (taxas ajustadas).

Rio de Janeiro: INCA. https://www.inca.gov.br/ estimativa/taxas-ajustadas/neoplasia-malignada-traqueia-dos-bronquios-e-dos-pulmoes Accessed May 20, 2020.

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