IASLC Lung Cancer News - V5, N2

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GLOBAL EDITION

LUNG CANCER

V5 / N2 / APRIL 2020

FOR THORACIC SPECIALISTS Read online at LungCancerNews.org g & Visit IASLC.org

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Grappling with Coronavirus (SARS-CoV-2)

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Partnering With Oncogene-Focused Patient Groups to Propel Research

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Decade of Progress Timeline: U.S. Drug Approvals

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Decade of Progress Timeline: Milestones in Lung Cancer Treatments

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Artificial Intelligence in Lung Cancer

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Deeper Dive: Disparities in Meeting Eligibility Criteria for Lung Cancer Screening

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A Cloud-Based Computerized System for the Korean Lung Cancer Screening Project

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PD-L1 Testing for Lung Cancer in 2019: Perspective From the IASLC Pathology Committee

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Liquid Biopsy’s Role in Marker Identification: An Interview With Dr. Martin Filipits

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Time to End the Debate on Genomic Testing in NSCLC

NEWS

I N T E R N AT I O N A L A S S O C I AT I O N F O R T H E S T U D Y O F L U N G C A N C E R E V O LV I N G S TA N D A R D S O F C A R E

Stunning Progress Achieved in Lung Cancer Treatment Over the Last Decade By Kara Nyberg, PhD

After decades of failed clinical trials and persistently dismal lung cancer survival outcomes, the 2010s breathed new life into the beleaguered field of lung cancer research. Treatment progress gained momentum and finally reached a tipping point in the mid-2010s, with the number of advances over the last 5 years outweighing all the advances in the 5 decades leading up to that point. As the field continues to race forward into the 2020s, it seems fitting to reflect back on how much the treatment of lung cancer has evolved over the past decade.

Surgery Surgical oncologists worldwide increasingly turned to video-assisted thoracic surgery (VATS) in the 2010s to manage early-stage lung cancer, with many centers now favoring this minimally invasive approach over open thoracotomy to reduce surgical morbidity.1 Multiple

observational studies and meta-analyses pointed to fewer postoperative complications and better short- and long-term survival with VATS lobectomy compared with open lobectomy. However, data from a large randomized trial supporting the advantage of this approach were heretofore lacking—that is, until the British VIOLET study, the largest randomized trial ever to compare clinical outcomes following VATS versus open surgery in patients with early-stage disease. At the end of 2019, the VIOLET investigators reported that patients who underwent VATS lobectomy experienced significantly fewer in-hospital complications compared with those who underwent open lobectomy (32.8% vs. 44.3%; p = 0.008), as well as a shorter length of stay (4 vs. 5 days; p = 0.008).2 Importantly, these benefits were attained without compromising early oncologic outcomes (i.e., R0 resection rates or lymph node upstaging) or increasing serious adverse events in the early postoperative period. Results

for patient-reported pain, quality of life, and disease recurrence at 1 year are still awaited.

Given its success in treating inoperable lung cancer, ongoing research is now focused on whether SABR can be used in lieu of surgery in early-stage disease. Some centers have explored other techniques to further decrease the invasiveness of surgery, including segmentectomy, single-port VATS, and roboticassisted thoracic surgery, with promising signals of success.

Radiotherapy For patients with early-stage NSCLC that is unsuitable for surgery, stereotactic ablative radiotherapy (SABR) offers an alternative. Both the American Society for Radiation Oncology3 and the European Society for Radiotherapy and continued on page 4

TA R G E T E D T H E R A P Y

Histologic Transformation From NSCLC to SCLC: A Mechanism of Resistance to Osimertinib and Other Agents Targeting EGFR Mutations By Denis Moro-Sibilot, MD, MSc

EGFR tyrosine kinase inhibitors (TKIs) are the standard of care for mutated EGFR NSCLC. Today, one of the burning questions is whether to select the most recent third-generation agent or to combine a first- or second-generation TKI with chemotherapy or antiangiogenic agents and reserve third generation inhibitors for patients who exhibit acquired resistance due to T790 mutations. Regardless of the first-line treatment chosen, resistance is, unfortunately, a nearly universal occurrence. The primary mechanism of resistance to first- and second-generation TKIs is represented by the appearance of the secondary resistance mutation T790M. This occurs approximately

50% to 60% of the time of circulating tumor DNA after treatment with first often limits the decision or second generation to re-biopsy, which is TKIs, but is extremely more complex to orgarare after treatment nize. Liquid biopsies with osimertinib in obviously do not allow the first-line setting. the diagnosis of SCLC Among other mechatransformation, which nisms, transformation requires tissue. Dr. Denis Moro-Sibilot into SCLC is a relatively Transformation to SCLC uncommon event, but it may occur at any time during occurs regardless of the generathe course of the disease, from the tion of TKI used, including osimertinib. first few months to several years after SCLC transformation occurs in 3% to the diagnosis of metastatic EGFR mt 10% of EGFR TKI‒resistant cases1,2; how(+) NSCLC, but the average transforever, this incidence is possibly underestimation time is approximately 13 to 18 mated due to the absence of or inability months after the start of TKI treatment.5,6 3,4 to re-biopsy at the time of progression. Although these tumors have the usual Moreover, the simplicity of the analysis histologic criteria of small cell carcino-

mas such as neuroendocrine differentiation, they differ from conventional SCLCs in that they occur in non-smokers or light smokers and frequently retain the original EGFR mutation, which is virtually never seen in de novo SCLC. More than two-thirds of SCLC transformations were observed in patients with EGFR exon 19 mutations (Table 1, page 3), whereas T790M resistance mutation is rarely observed in transformed SCLCs, even if it was present in the patient’s previous specimens, suggesting that this mutation may appear in a clone that is distinct from the clone that transforms to SCLC. Losses of P53 and RB1 with inactivation of the two key alleles were identified in a majority of transformed SCLCs. A continued on page 3


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