CheckMate-577 clinical trial results show nivolumab adjuvant therapy increases disease-free survival over placebo in patients with gastroesophageal junction (GEJ) cancer or esophageal cancer.
Esophageal cancer is a public and clinical health concern because of its aggressive disease course and a 5-year overall survival rate of <20%.1 The main histological subtypes are squamous-cell carcinoma (SCC) and adenocarcinoma, with SCC accounting for most cases.1 The standard-of-care treatment for patients with locally advanced resectable esophageal cancer or gastroesophageal junction (GEJ) cancer is neoadjuvant chemoradiotherapy followed by surgery. In patients who do not have a pathological complete response to treatment, and in those with lymph node–positive disease, the risk for recurrent disease is high. Surveillance is the standard of care for these patients. However, clinical trials have demonstrated that nivolumab, an anti–PD-L1 monoclonal antibody, improves survival times in patients with advanced gastroesophageal cancer who had previously received treatment.
The CheckMate-577 clinical trial evaluated the use of nivolumab in patients with recurrence of esophageal or GEJ cancer after neoadjuvant chemoradiotherapy and surgery. Adults with stage 2 or 3 esophageal or GEJ cancer who had received neoadjuvant chemoradiotherapy and surgery and had residual pathological disease with ypT1 or ypN1 tumor and node classification were eligible for the study. More than half of the study participants had positive lymph node disease. Study randomization to nivolumab or placebo took place 4 to 16 weeks after surgery.
Nivolumab was given at a dose of 240 mg intravenously every 2 weeks for 16 weeks, then starting on week 17 at a dose of 480 mg every 4 weeks, to 532 participants. Placebo was given to 262 participants. Nivolumab or placebo administration continued until cancer recurred, toxicity became intolerable, or the patient withdrew consent.
The study primary end point was disease-free survival (DFS), with nivolumab use conferring a median DFS of 22.4 months. The patients who received placebo had a median DFS of 11.0 months. Patients who received nivolumab had a significantly longer DFS that was sustained across multiple study subgroups. The nivolumab group also had less frequent disease recurrence.
Disease-free survival was greater in patients who began nivolumab ≥10 weeks after surgery compared with those who started nivolumab <10 weeks after surgery. Treatment-related adverse events (AEs) were more common in the patients who received nivolumab, with 13% of these patients experiencing grade 3 or 4 events compared with 6% of the placebo group. Diarrhea, fatigue, pruritus, and rash were the most common AEs in the nivolumab group and diarrhea and fatigue were the most common in the placebo group. AEs caused 9% of the nivolumab group and 3% of the placebo group to discontinue treatment.
Nivolumab adjuvant therapy conveyed a significant improvement in DFS in patients in this study. On May 20, 2021, the FDA approved nivolumab for patients with completely resected esophageal or GEJ cancer with residual pathologic disease who have received neoadjuvant chemoradiotherapy.
Source: Kelly RJ, Ajani JA, Kuzdzal J, et al. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer. N Engl J Med. 2021;384:1191-1203.
- Huang J, Koulaouzidis A, Marlicz W, et al. Global burden, risk factors, and trends of esophageal cancer: an analysis of cancer registries from 48 countries. Cancers (Basel). 2021;13:141.