The FDA granted a new indication for nivolumab (Opdivo, Bristol Myers Squibb) for the treatment of patients with completely resected esophageal or gastroesophageal junction (GEJ) cancer with residual pathologic disease who have received neoadjuvant chemoradiotherapy (CRT).

“Locally advanced esophageal and gastroesophageal junction cancers are aggressive tumor types that often require multiple approaches to address the disease, including chemotherapy, radiation and surgery. 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,” according to Ronan J. Kelly, MD, MBA, an investigator on the CheckMate-577 trial on which the approval was based. In the trial, “we saw a doubling in median disease-free survival compared to placebo, which suggests that [nivolumab] could become a new standard of care for these patients,” added Dr. Kelly, the director of the Baylor Scott & White Charles A. Sammons Cancer Center, in Dallas.

Efficacy was evaluated in the phase 3 CheckMate-577, a multicenter, randomized double-blind trial in 794 patients with completely resected (negative margins) esophageal or GEJ cancer who had residual pathologic disease following concurrent CRT. Patients were randomly assigned in a 2:1 fashion to receive either 240 mg of nivolumab or placebo every two weeks for 16 weeks, followed by 480 mg of nivolumab or placebo every four weeks beginning at week 17, for up to one year of treatment.

The main outcome measure was disease-free survival (DFS), defined as the time between randomization date and the date of first recurrence (local, regional or distant from the primary resected site), or death from any cause, as assessed by the investigator prior to subsequent anticancer therapy.

In the trial, median DFS was twice as long among patients who received nivolumab as in those who received placebo (22.4 months [95% CI, 16.6-34.0 months] vs. 11 months [95% CI, 8.3-14.3 months]). Nivolumab reduced the risk for disease recurrence or death by 31% compared with placebo (hazard ratio [HR], 0.69; 95% CI, 0.56-0.85; P=0.0003). 

In an exploratory analysis, among 563 patients with adenocarcinoma (70.9%), median DFS was 19.4 months (95% CI, 15.9-29.4 months) with nivolumab versus 11.1 months (95% CI, 8.3-16.8 months) with placebo (unstratified HR, 0.75; 95% CI, 0.59-0.96). Among 230 patients with squamous cell carcinoma (29%), median DFS was 29.7 months (95% CI, 14.4 to NE) with nivolumab versus 11.0 months (95% CI, 7.6-17.8 months) with placebo (unstratified HR, 0.61; 95% CI, 0.42-0.88) (N Engl J Med 2021;384:1191-203).

The most common adverse reactions in patients receiving nivolumab are 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.

For more information, view the full prescribing information for nivolumab.

Nivolumab received orphan drug designation for this indication and is the only immunotherapy approved in this patient population. 

—GEN Staff

Based on press releases from FDA and Bristol Myers Squibb.