Adjuvant nivolumab improved disease-free survival (DFS) compared with placebo among patients with stage II or III esophageal or gastroesophageal junction (GEJ) cancers with residual pathologic disease after resection, according to the results of the phase 3 CheckMate 577 trial (ClinicalTrials.gov Identifier: NCT02743494) published in the New England Journal of Medicine.
Residual pathologic disease remains after neoadjuvant chemotherapy and resection among 70% to 75% of patients with esophageal or GEJ cancers, and the risk of recurrence is particularly high for these patients. “Adjuvant treatments to improve outcomes are clearly needed; however, none has proved to be effective,” the authors stated.
The double-blind, phase 3 CheckMate 577 trial randomly assigned 532 patients with resected stage II or III esophageal or GEJ cancer 2:1 to receive nivolumab or placebo for up to 1 year. All patients underwent neoadjuvant chemotherapy and resection and were considered free of disease but had residual pathologic disease within the tumor. The primary endpoint of the study was DFS, and the secondary endpoint was overall survival (OS) at 1, 2, and 3 years.
At baseline, the median age was 62 years, 85% were male, and the majority of patients were White (82%), followed by 15% who were Asian; and the remaining were Black, other, or not reported. Tumor histology was adenocarcinoma in 71% and squamous cell carcinoma in 29% of the study patients.
Adjuvant nivolumab significantly prolonged DFS with a median of 22.4 months compared with 11.0 months for placebo (hazard ratio [HR], 0.69; 95% CI, 0.56-0.86; P <.001). Benefit with nivolumab was observed regardless of histology, PD-L1 tumor expression, or doses of neoadjuvant radiation therapy.
Both distant and locoregional recurrences occurred less frequently with nivolumab. Distant recurrence occurred in 29% and 39% of patients in the nivolumab and placebo groups, respectively, and locoregional recurrence occurred in 12% and 17%, respectively.
Nivolumab resulted in a median distant metastasis–free survival of 28.3 months compared with 17.6 months for placebo (HR, 0.74; 95% CI, 0.60-0.92).
Treatment-related adverse events developed among 13% of patients who received nivolumab and 6% of patients who received placebo. Adverse events that led to treatment discontinuation occurred in 9% and 3% of patients in the nivolumab and placebo groups, respectively.
The authors concluded that “In patients with resected esophageal or [GEJ] cancer after neoadjuvant chemotherapy, nivolumab adjuvant therapy was associated with a significantly longer [DFS] than placebo.”
Disclosures: This clinical trial was supported by Bristol Myers Squibb and Ono Pharmaceutical. Please see the original reference for a full lust of authors’ affiliations.
Kelly RJ, Ajani JA, Kuzdzal J, et al. CheckMate 577 Investigators. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer. N Engl J Med. 2021;384:1191-1203.