Nivolumab Receives New Indication for dMMR and MSI-H Metastatic Colorectal Cancer

October 2017 - FDA Approvals, News & Updates, Web Exclusives


On July 31, 2017, the FDA accelerated the approval of a new indication for nivolumab (Opdivo; Bristol-Myers Squibb) for the treatment of patients aged ≥12 years with mismatch repair–deficient (dMMR) and microsatellite instability–high (MSI-H) metastatic colorectal cancer (CRC) that progressed after treatment with fluoropyrimidine, oxaliplatin, and irinotecan.

The FDA approval of this new indication was based on a single-arm, open-label, multicenter clinical trial of 53 patients with locally determined dMMR or MSI-H metastatic CRC whose disease progressed during or after, or who could not tolerate, fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. All patients had received ≥1 treatments containing 1 of the 3 therapies. In the study leading to this approval, the patients received intravenous nivolumab 3 mg/kg every 2 weeks until unacceptable toxicity or radiographic progression.

The objective response rate was 28% (N = 15); of these 15 responses, 1 was a complete response and 14 were partial responses. In 67% of patients, the responses lasted ≥6 months. Among the 74 patients in the overall population, there was an objective response rate of 32%.

The study did not include a pediatric population; nivolumab’s dosing is 240 mg every 2 weeks in patients aged ≥12 years with MSI-H or dMMR metastatic CRC, which was determined based on results in adults.

The most common (≥20%) adverse events seen with nivolumab monotherapy include fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, upper respiratory tract infection, and pyrexia. As a condition of the accelerated approval of this indication, further trials must confirm the clinical benefit of nivolumab in this setting.