The Food and Drug Administration (FDA) has approved Opdivo® (nivolumab) for the adjuvant treatment of completely resected esophageal or gastroesophageal junction (GEJ) cancer with residual pathologic disease in patients who have received neoadjuvant chemoradiotherapy (CRT).
The approval was based on data from the randomized, multicenter, double-blind phase 3 CheckMate-577 trial (ClinicalTrials.gov: NCT02743494) which included 794 adults with completely resected esophageal or GEJ cancer who had residual pathologic disease following neoadjuvant CRT. Patients were randomly assigned 2:1 to receive nivolumab 240mg or placebo by intravenous (IV) infusion over 30 minutes every 2 weeks for 16 weeks followed by nivolumab 480mg or placebo every 4 weeks until disease progression or unacceptable toxicity for up to 1 year.
The primary endpoint was disease-free survival (DFS) defined as the time between the date of randomization and the date of first recurrence (local, regional, or distant from the primary resected site) or death, from any cause.
Results demonstrated that patients treated with nivolumab achieved a statistically significant improvement in median DFS of 22.4 months (95% CI, 16.6-34) vs 11 months for placebo (95% CI, 8.3-14.3). Nivolumab reduced the risk of disease recurrence or death by 31% vs placebo (hazard ratio [HR] 0.69; 95% CI, 0.56-0.85; P =.0003). The DFS benefit was observed regardless of tumor PD-L1 expression and histology.
In an exploratory analysis, among patients with adenocarcinoma (n=563), the median DFS was 19.4 months (95% CI, 15.9-29.4) for nivolumab vs 11.1 months (95% CI, 8.3-16.8) for placebo, with an unstratified HR of 0.75 (95% CI, 0.59-0.96). Among patients with squamous cell carcinoma (n=230), the median DFS was 29.7 months (95% CI, 14.4-not estimable) for nivolumab vs 11 months (95% CI, 7.6-17.8) for placebo, with an unstratified HR of 0.61 (95% CI, 0.42-0.88).
As for safety, the most common adverse reactions (incidence greater than or equal to 20%) were fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, upper respiratory tract infection, pyrexia, headache, abdominal pain, and vomiting.
“Even after neoadjuvant CRT followed by surgery, there may be a high risk of recurrence for patients who do not achieve a pathologic complete response. In the CheckMate -577 trial, we saw a doubling in median disease-free survival compared to placebo, which suggests that Opdivo could become a new standard of care for these patients,” said Ronan J. Kelly MD, MBA, director, Baylor Scott & White Charles A. Sammons Cancer Center, and W.W. Caruth Jr. Endowed Chair of Immunology at Baylor University Medical Center.
- U.S. Food and Drug Administration approves Opdivo® (nivolumab) as adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer in patients who have received neoadjuvant chemoradiotherapy. [press release]. Princeton, NJ: Bristol Myers Squibb; May 20, 2021.
- FDA approves nivolumab for resected esophageal or GEJ cancer. [press release]. Silver Spring, MD: US Food and Drug Administration; May 20, 2021.
- Opdivo [package insert]. Princeton, NJ: Bristol Myers Squibb; 2021.