Clinical Pearls & Morning Reports
Kelly et al. conducted CheckMate 577, a global, randomized, double-blind, placebo-controlled phase 3 trial that evaluated the use of a checkpoint inhibitor as adjuvant treatment after neoadjuvant chemoradiotherapy followed by surgery for esophageal or gastroesophageal junction cancer. Read the NEJM Original Article here.
Q: Is the incidence of esophageal cancer stable?
A: Esophageal cancer, the seventh most common cancer globally, accounts for more than half a million deaths each year. The incidence of esophageal squamous-cell carcinoma, the most common histologic type, has been stable, whereas the incidences of esophageal and gastroesophageal junction adenocarcinomas continue to increase in Western countries.
Q: How effective is neoadjuvant chemoradiotherapy followed by surgery for resectable locally advanced esophageal or gastroesophageal junction cancer?
A: Neoadjuvant chemoradiotherapy followed by surgery is a well-established standard of care for resectable, locally advanced esophageal or gastroesophageal junction cancer. However, a pathological complete response is often not achieved, and most patients have a poor prognosis. Currently, the standard management after neoadjuvant chemoradiotherapy and surgery is surveillance, and the development of an effective adjuvant treatment has been an elusive goal.
A: In the CheckMate 577 trial, nivolumab adjuvant therapy showed superior efficacy over placebo in the primary end point of disease-free survival. The trial population consisted of patients with residual pathological disease and a high risk of recurrence, which is reported in 70 to 75% of patients with esophageal or gastroesophageal junction cancer after neoadjuvant chemoradiotherapy and surgery. More than half the trial patients had lymph node–positive disease, which is associated with particularly poor outcomes. Despite the poor prognostic factors in these patients, nivolumab was associated with significant improvement in disease-free survival, with a 31% reduction in the risk of recurrence or death, and the median disease-free survival was twice as long in the nivolumab group as in the placebo group. Similar hazard ratios for disease recurrence or death with tumor-cell PD-L1 expression either below 1% or 1% or higher indicate that adjuvant nivolumab was similarly effective regardless of tumor-cell PD-L1 expression.
A: In addition to a disease-free survival benefit, the risk of distant recurrence or death was 26% lower and distant metastasis–free survival was 10.7 months longer with adjuvant nivolumab than with placebo. The trial is ongoing, and an analysis of the secondary end point of overall survival is planned. The safety profile of adjuvant nivolumab was in line with that in previous trials involving patients with gastroesophageal and other solid tumors. Serious adverse events related to nivolumab and adverse events leading to discontinuation of the trial regimen in the nivolumab group were reported in less than 10% of the patients. The most common adverse events of any grade that were considered to be related to the trial regimen were fatigue, diarrhea, pruritus, and rash in patients receiving nivolumab and diarrhea and fatigue in those receiving placebo.