The FDA has approved nivolumab (Opdivo, Bristol Myers Squibb) with ipilimumab (Yervoy, Bristol Myers Squibb) for adult and pediatric patients 12 years of age and older with unresectable or metastatic microsatellite instability−high (MSI-H) or mismatch repair−deficient (dMMR) colorectal cancer (CRC). The FDA also converted the accelerated approval to regular approval for single-agent nivolumab for adult and pediatric patients 12 years of age and older with MSI-H or dMMR metastatic CRC, that has progressed following fluoropyrimidine, oxaliplatin and irinotecan.

The efficacy of nivolumab with ipilimumab was evaluated in CHECKMATE-8HW (ClinicalTrials.gov Identifier: NCT04008030), a randomized, three-arm, open-label trial in immunotherapy-naive patients with unresectable or metastatic CRC with known MSI-H or dMMR status. Patients were randomized to receive one of the following treatments:
• nivolumab 240 mg every three weeks and ipilimumab 1 mg/kg every three weeks for a maximum of four doses, then nivolumab 480 mg every four weeks;
• nivolumab 240 mg every two weeks for six doses, then nivolumab 480 mg every four weeks; or
• investigator’s choice of chemotherapy.

The major efficacy outcome measure was progression-free survival (PFS), assessed by blinded independent central review per RECIST v1.1 in patients with centrally confirmed MSI-H/dMMR status in the following pre-specified settings:
• First-line setting: nivolumab plus ipilimumab versus chemotherapy,
• All lines: nivolumab plus ipilimumab versus nivolumab alone.

The analysis of nivolumab plus ipilimumab versus chemotherapy in the first-line setting was conducted in 255 patients with centrally confirmed MSI-H/dMMR status of 303 patients based on local testing. The median PFS was not reached (95% CI, 38.4 to not estimable [NE]) in the nivolumab plus ipilimumab arm and 5.8 months (95% CI, 4.4-7.8 months) in the chemotherapy arm (hazard ratio, 0.21; 95% CI, 0.14-0.32; P<0.0001). Comparative results for overall response rate (ORR) and overall survival (OS) between arms were not available at the time of the interim PFS analysis due to statistical testing strategy.

The analysis of nivolumab plus ipilimumab versus nivolumab (all lines) was conducted in 582 patients with centrally confirmed MSI-H/dMMR status of 707 patients based on local testing. The median PFS was not reached (95% CI, 53.8 months to NE) in the nivolumab plus ipilimumab arm and 39.3 months (95% CI, 22.1 months to NE) in the nivolumab arm (hazard ratio, 0.62; 95% CI, 0.48-0.81; P=0.0003). The ORR was 71% (95% CI, 65%-76%) in the nivolumab plus ipilimumab arm and 58% (95% CI, 52%-63%) in the nivolumab arm (P=0.0011). The comparative results for OS between arms were not available at the interim PFS analysis due to statistical testing strategy.

The most common adverse reactions reported in 20% or more of patients treated with nivolumab with ipilimumab were fatigue, diarrhea, pruritus, abdominal pain, musculoskeletal pain and nausea. The most common adverse reactions reported in 20% or more of patients treated with nivolumab as a single agent were fatigue, diarrhea, abdominal pain, pruritus and musculoskeletal pain.

The full prescribing information for nivolumab and ipilimumab will be posted on Drugs@FDA.

—GEN Staff

Based on a press release from the FDA. 

Originally published by our sister publication Clinical Oncology News