On May 20, the U.S. Food and Drug Administration (FDA) approved nivolumab (Opdivo) for patients with completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease who have received neoadjuvant chemoradiotherapy.
Efficacy was evaluated in CheckMate 577 (ClinicalTrials.gov identifier NCT02743494), a randomized, multicenter, double-blind trial in 794 patients with completely resected (negative margins) esophageal or gastroesophageal junction cancers who had residual pathologic disease following concurrent chemoradiotherapy. Patients were randomly assigned 2:1 to receive either nivolumab at 240 mg or placebo every 2 weeks for 16 weeks, followed by 480 mg of nivolumab or placebo every 4 weeks beginning at week 17 for up to 1 year of treatment.
The main efficacy outcome measure was disease-free survival, defined as the time between random assignment date and the first recurrence (local, regional, or distant from the primary resected site) date, or death from any cause as assessed by the investigator prior to subsequent anticancer therapy.
CheckMate 577 demonstrated a statistically significant improvement in disease-free survival for patients receiving nivolumab as compared to those in the placebo arm. The median disease-free survival was 22.4 months (95% confidence interval [CI] = 16.6–34.0) vs 11 months (95% CI = 8.3–14.3), respectively (hazard ratio = 0.69, 95% CI = 0.56–0.85, P = .0003). The disease-free survival benefit was observed regardless of tumor PD-L1 expression and histology.
The most common adverse reactions (incidence ≥ 20%) in patients receiving nivolumab 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.
The recommended nivolumab dose for adjuvant treatment of resected esophageal or gastroesophageal junction cancer is 240 mg every 2 weeks or 480 mg every 4 weeks for a total treatment duration of 1 year. Both doses are administered as 30-minute intravenous infusions.