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
Would you ever consider adjuvant chemotherapy rather than adjuvant immunotherapy after the publication of the CM-577 results? If so, in which pop...
New comment by Medical Oncologist at Mary Lanning Healthcare Morrison Cancer Center/University of Nebraska Medical Center Adjunct Faculty ( February 9, 2022)
If the question was, "For a patient with distal esophageal adenocarcinoma with residual disease after perioperative chemotherapy followed by surgery, would you recommend adjuv...
NCCN recommends perioperative FLOT or FOLFOX vs. neoadjuvant chemoRT with Carboplatin/Paclitaxel or FOLFOX.Does CM-577 and the approval of nivolumab p...
New answer by Radiation Oncologist at Coastal Carolina Radiation Oncology (January 22, 2022)
Neoadjuvant chemo and targeted therapy, as local control is better with neoadjuvant treatment and then surgery.
CheckMate 577 only included patients with R0 resection.For R1 resections, guidelines suggest observation vs re-resection only.
New answer by Medical Oncologist at Harvard Medical School (November 14, 2021)
While CheckMate 577 was not designed to answer this question, my inclination is that adjuvant nivolumab could help patients who had an R1 resection and I would strongly consid...
Are there other treatment variations by clinical subsets (eg tumor location, histology, stage II vs III, other biomarkers) seen in CM577 or other data...
New answer by Medical Oncologist at University of Washington Medical Center (November 16, 2021)
Yes, the CM 577 trial showed benefit across subgroups by tumor PDL1 status (tumor PDL1 expression < 1% or >= 1%). Thus, I would not use PDL1 status in the decision makin...
What factors would influence your approach?
New answer by Medical Oncologist at University of Washington Medical Center (November 16, 2021)
This is a challenging scenario and in general, I would still favor use of chemo+immunotherapy in patients with Her2 NEG disease who have CPS 5 or higher or are dMMR, even if t...
Based on CheckMate 577?Is DFS endpoint sufficient to establish SOC or is OS benefit needed?
New comment by Medical Oncologist at Uniformed Services University of the Health Sciences (USUHS) ( March 7, 2023)
Dr. @Kelly - would you offer adjuvant nivolumab for those who DID obtain a pCR?
For patients who have already undergone trimodality treatment, what time frame do you consider for adjuvant IO?
New answer by Medical Oncologist at Memorial Sloan Kettering Cancer Center (January 4, 2022)
I would not. In CheckMate 577, patients could receive nivolumab up to 4 months following surgery. In a patient who is a year out from surgery, we cannot possibly know the bene...
Residual GEJ mass and progression in local lymph nodes after carbo+taxol chemoRT without distant metastases.
New answer by Medical Oncologist at Memorial Sloan Kettering Cancer Center (May 4, 2022)
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 ...
New answer by Medical Oncologist at Duke University (May 10, 2022)
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 ...
New comment by Medical Oncologist at Joliet Oncology Hematology Associates ( July 21, 2022)
Excellent commentary, this is extremely helpful. However, in the community setting, this recommendation is not always followed. As med onc we need to do a better job in educat...