Opdivo plus Yervoy Approved for MSI-H or dMMR Colorectal Cancer

October 2018, Vol 8, No 10 - FDA Approvals, News & Updates


On July 10, 2018, the FDA accelerated the approval of the combination of nivolumab and ipilimumab (Opdivo and Yervoy; Bristol-Myers Squibb) for the treatment of patients aged ≥12 years with metastatic c­o­lorectal cancer (CRC) associated with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) that progressed after chemotherapy with fluoropyrimidine, oxaliplatin, and irinotecan.

This approval was based on an open-label, multicenter clinical trial of 82 patients with dMMR or MSI-H metastatic CRC that progressed during or after treatment with the fluoropyrimidine, oxaliplatin, and irinotecan regimen. All patients received ipilimumab 1 mg/kg and nivolumab 3 mg/kg every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg monotherapy every 2 weeks, until disease progression or unacceptable toxicity.

The overall response rate was 46%, including 3 complete responses and 35 partial responses. The response rate with the combination was higher than with nivolumab monotherapy in a separate cohort of 58 patients with dMMR or MSI-H metastatic CRC that progressed during or after chemotherapy.

Similarly, the rate of ≥6 months duration of response was higher with the combination than with nivolumab monotherapy (89% vs 67%, respectively).

The most common (≥20%) adverse reactions with ipilimumab and nivolumab are fatigue, diarrhea, pyrexia, musculoskeletal pain, abdominal pain, pruritus, nausea, rash, dyspnea, decreased appetite, and vomiting.