N Engl J Med 2021-04-01
Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer.
Abstract
Background
No adjuvant treatment has been established for patients who remain at high risk for recurrence after neoadjuvant chemoradiotherapy and surgery for esophageal or gastroesophageal junction cancer.
Methods
We conducted CheckMate 577, a global, randomized, double-blind, placebo-controlled phase 3 trial to evaluate a checkpoint inhibitor as adjuvant therapy in patients with esophageal or gastroesophageal junction cancer. Adults with resected (R0) stage II or III esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy and had residual pathological disease were randomly assigned in a 2:1 ratio to receive nivolumab (at a dose of 240 mg every 2 weeks for 16 weeks, followed by nivolumab at a dose of 480 mg every 4 weeks) or matching placebo. The maximum duration of the trial intervention period was 1 year. The primary end point was disease-free survival.
Results
The median follow-up was 24.4 months. Among the 532 patients who received nivolumab, the median disease-free survival was 22.4 months (95% confidence interval [CI], 16.6 to 34.0), as compared with 11.0 months (95% CI, 8.3 to 14.3) among the 262 patients who received placebo (hazard ratio for disease recurrence or death, 0.69; 96.4% CI, 0.56 to 0.86; P<0.001). Disease-free survival favored nivolumab across multiple prespecified subgroups. Grade 3 or 4 adverse events that were considered by the investigators to be related to the active drug or placebo occurred in 71 of 532 patients (13%) in the nivolumab group and 15 of 260 patients (6%) in the placebo group. The trial regimen was discontinued because of adverse events related to the active drug or placebo in 9% of the patients in the nivolumab group and 3% of those in the placebo group.
Conclusions
Among patients with resected esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy, disease-free survival was significantly longer among those who received nivolumab adjuvant therapy than among those who received placebo. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 577 ClinicalTrials.gov number, NCT02743494.).
Related Questions
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Would you give adjuvant chemotherapy to a distal esophageal adenocarcinoma T3NxM0 who s/p chemo-radiation and esophagectomy, had a complete pathologic response (ypT0N0)?
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Are there any situations where you would consider neoadjuvant chemoradiation as opposed to chemoimmunotherapy for patients with resectable NSCLC prior to surgical resection?
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When planning to give adjuvant nivolumab for esophageal cancer, would you be comfortable with nivolumab with q4 weekly dosing as opposed to q2 weekly dosing?
I generally start with Q2 week dosing - as per the BMS CheckMate 577 protocol - so that I can make sure that there is not any immediate toxicity. In the study, the dosing was Q2 weeks until 16 weeks and then it moved to Q4 weeks. If a patient is doing well, I have moved to Q4 week dosing at 8 weeks ...
How would you treat a patient with T4N1M0 GEJ adenocarcinoma with local progression after concurrent chemoRT who still has resectable disease?
This is a tricky but thankfully rare scenario.My answer depends on the nature of the local progression. The more favorable situation involves local persistence of the primary tumor with a modest increase in locoregional lymph nodes. This situation would essentially represent a lack of response to ch...
Would you offer adjuvant immunotherapy to a patient with esophageal cancer who completed neoadjuvant chemo+RT followed by surgery a year ago?
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How does use of adjuvant nivolumab impact your subsequent use of immunotherapy + chemo in a PDL1+ GEJ cancer with metastatic relapse?
This is an extremely important, and practical question, which, unfortunately, we have very limited data on. Clearly, more study is needed here so that we can develop more carefully tailored therapies for our patients. However, for now, my approach is primarily based on the timing of metastatic disea...
Can CM577 regimen of adjuvant nivolumab s/p neoadjuvant chemoRT with residual disease following surgery be extrapolated to patients with R1 resection unable to undergo re-resection?
This is an excellent question and, of course, one for which there are no data. So, unburdened by data, I'm free to offer my personal opinion. I think all of us would value other comments and responses to this question as well.I think that this question also applies to those patients who achieve a cl...
Can the results of Checkmate 577 be applied to patients who do not undergo surgery following chemoradiation because of a clinical complete response?
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