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IN THE NEWS
GENERAL SURGERY NEWS / MAY 2021
First Look: The Society of Surgical Oncology International Conference All articles by KATE O’ROURKE
Nivolumab Shows Promise for Resected Esophageal, GE Junction Cancers
Medicaid Expansion Associated With Earlier Diagnosis of Gastric Cancer
DCIS Biological Risk Signature Predicts Recurrence, Radiation Benefit
Adjuvant nivolumab is the first therapy to provide a statistically significant and clinically meaningful improvement in disease-free survival in patients with resected esophageal and gastroesophageal junction cancer. This news comes from research presented at the Society of Surgical Oncology 2021 International Conference on Surgical Cancer Care (abstract 94). “The risk of recurrence after neoadjuvant chemoradiation therapy followed by surgery (trimodality therapy) remains high in esophageal or gastroesophageal junction cancer and there is no established adjuvant treatment,” said Guillaume Piessen, MD, PhD, of the University of Lille, Claude Huriez University Hospital, in Lille, France, who presented the findings. Nivolumab (Opdivo, Bristol Myers Squibb) offers a new standard of care in these patients, Dr. Piessen said. The findings come from the CheckMate 577 trial, which is the first global, phase 3, randomized, doubleblind study to report the efficacy and safety of a checkpoint inhibitor in the adjuvant setting after trimodality therapy for esophageal or gastroesophageal junction cancer (N Engl J Med 2021;384:1191-1203). The trial enrolled 794 adults, of whom 532 received nivolumab and 262 were given placebo. Patients who had resected stage II/III esophageal/gastroesophageal junction cancer and received neoadjuvant chemoradiation therapy and had residual pathologic disease were randomized 2:1 to nivolumab 240 mg or placebo every two weeks for 16 weeks, followed by nivolumab 480 mg or placebo every four weeks. Maximum treatment duration was one year. The primary end point was diseasefree survival. Approximately 70% of patients had adenocarcinoma and almost 60% had a pathologic lymph node status of ypN1 or higher in both groups. Patients receiving nivolumab were predominantly male (84%) and white (81%), with an Eastern Cooperative Oncology Group (or ECOG) performance status of 0 (58%). They also had predominantly stage III disease (66%) and received a diagnosis of adenocarcinoma (71%). The median age was 62 years. At a prespecified interim analysis, adjuvant nivolumab was significantly associated with improvement in DFS versus placebo (hazard ratio, 0.69; 96.4% CI, 0.560.86; P=0.0003). Median disease-free survival was doubled. Most treatment-related adverse events were grade 1 or 2. The incidence of serious adverse reactions leading to discontinuation was 9% or lower with nivolumab and 3% with placebo. The majority of treatment-related adverse events with an immunologic etiology were low grade, with grade 3/4 events occurring in fewer than 1% of patients in the nivolumab group. Based on the promising data from the trial, the FDA accepted the supplemental Biologics License Application for nivolumab for the treatment of patients with resected esophageal/gastroesophageal junction cancer in the adjuvant setting, after neoadjuvant chemoradiation therapy. The agency also granted the application priority review.
According to research presented at the Society of Surgical Oncology 2021 International Conference on Surgical Cancer Care, Medicaid expansion caused a decrease in uninsured patients and led to an earlier diagnosis of gastric cancer with an associated increase in oneyear survival (abstract 95). “Increased health care access may be associated with a shift toward earlier diagnosis with improved outcomes in gastric cancer,” said study author Clara Zhu, MD, of Cooper University Health Care in Camden, N.J., who presented the findings. According to Dr. Zhu, the 2014 Medicaid expansion was intended to improve patient access to care. Some states elected to expand Medicaid, while others opted not to expand the program. Dr. Zhu and her colleagues hypothesized that Medicaid expansion was associated with earlier diagnosis and improved outcomes in gastric cancer. To find out, Dr. Zhu’s research team turned to the National Cancer Database to identify patients with a new primary diagnosis of gastric cancer between 2006 and 2016. The researchers compared states that expanded Medicaid in 2014 to those that did not, excluding states that expanded earlier or later than 2014 and patients older than 64 years. Her research compared the pre- and post-expansion intervals 2012-2013 and 2015-2016. The study cohort included 20,639 patients. Expansion states demonstrated a significant reduction in uninsured patients from 7.0% to 2.7% (P<0.01) compared with non-expansion states (14.2%-10.9%; P=not significant [NS]). The researchers identified an increase in patients diagnosed with stage 0 to II gastric cancer from 38% to 41.5% (P<0.01) in expansion states, but found no change at 38.9% in nonexpansion states. Patients 50 years of age and older diagnosed with stage 0 to II gastric cancer increased in expansion states from 38.2% to 42.5% (P<0.01), and in non-expansion states from 39.3% to 39.9% (P=NS). Uninsured and Medicaid patients diagnosed with stage 0 to II gastric cancer increased in expansion states from 32.4% to 37.8% (P=0.01), and decreased in nonexpansion states from 29.7% to 27.3% (P=NS). Patients receiving treatment rose from 91.6% to 92.2% in expansion states (P=0.01) and from 89.6% to 89.7 (P=NS) in non-expansion states. Rates of treatment for uninsured and Medicaid patients rose in 87.0% to 90.3% in expansion states (P=0.01) and from 83.9% to 84.9% in nonexpansion states (P=NS). Twelve-month survival for patients in expansion states rose from 68.1% to 70.6% (P=0.03), but decreased from 65.2% to 65.1% (P=NS) in non-expansion states.
Women with ductal carcinoma in situ and elevated commercial DCISion scores (DS) had a significantly higher risk for ipsilateral breast events and a greater relative benefit from radiation therapy than women with lower scores. These findings come from research recently presented at the Society of Surgical Oncology 2021 International Conference on Surgical Cancer Care (abstract 5). Radiation therapy after breast-conserving surgery for DCIS is known to reduce the risk for ipsilateral breast events without altering survival, but its use varies widely due to differing assessments of the risk–benefit ratio. Precise assessment of postsurgical radiation therapy benefit would allow individualized treatment decisions. In the new study, Bruce Mann, MBBS, PhD, FRACS, of Royal Melbourne Hospital, in Victoria, Australia, and his colleagues conducted a validation of a commercially available biological risk signature, DCISionRT (PreludeDx), to assess ipsilateral breast events risk after breast-conserving surgery and the benefit of radiation therapy. Using a retrospective Australian cohort, Dr. Mann identified 183 women with DCIS who met eligibility criteria. Medical records were reviewed to collect data on treatment and outcomes, and tissue specimens were provided to the PreludeDx CLIA lab for blinded testing of a panel of biomarkers (HER2, PR, Ki-67, COX2, p16/INK4, FOXA1 and SIAH2) scored by board-certified pathologists, and determination of the patented DS. The researchers used a multivariate Cox proportional hazards analysis to assess the prognostic effect of DS for ipsilateral breast events risk. They adjusted for adjuvant treatments. The predictive effect of DS for radiation therapy benefit on ipsilateral breast events was assessed by the multivariate analysis, including the radiation therapy‒DS interaction. Of the 183 women in the study, 72 received radiation therapy and 66 received endocrine therapy. The total cohort had a five-year ipsilateral breast events risk of 10%. By treatment group, women given radiation therapy had a 4% risk and those treated without radiation therapy had a 14% risk. Among patients treated without radiation therapy, those with a low DS had a 7% rate of ipsilateral events, while those with elevated DS had a 23% rate. After breast-conserving surgery without endocrine therapy, patients with low DS had a nonsignificant difference of 2% with and without radiation therapy, while those with elevated DS had a highly significant 27% difference, indicating tumor radiation sensitivity. Findings were similar when all patients were included—2% and 20% absolute differences with radiation therapy. “This validation in a contemporary cohort supports previous findings that DCISionRT provides prognostic and predictive information to allow personalized ■ treatment decisions,” Dr. Mann said.
Dr. Piessen reported no relevant financial disclosures.
Dr. Zhu reported no relevant financial disclosures.
Dr. Mann reported no relevant financial disclosures.
