FDA Approves Nivolumab in MSI-H or dMMR Metastatic Colorectal Cancer


Today, the U.S. Food and Drug Administration (FDA) approved nivolumab (Opdivo) injection for intravenous use for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. Approval for this indication has been granted under accelerated approval based on overall response rate and duration of response found in the CheckMate 142 trial.

“Patients with metastatic colorectal cancer who have dMMR or MSI-H tumors are less likely to respond to conventional chemotherapy,” said Heinz-Josef Lenz, MD, FACP, J. Terrence Lanni Chair in Gastrointestinal Cancer Research, University of Southern California. “While the challenges of treating these patients have been significant, tumors characterized by these biomarkers are immunogenic. Therefore, advances in immunotherapy research are encouraging in presenting new treatment options for appropriate patients with MSI-H metastatic colorectal cancer.”

“As the third most common type of cancer in the United States, our view is that colorectal cancer—particularly for those with dMMR or MSI-H metastatic disease—has been in need of new research and treatments.The approval of nivolumab for appropriate patients with this disease gives the community more hope,” said Michael Sapienza, Chief Executive Officer of the Colon Cancer Alliance.

CheckMate 142

CheckMate 142 is a phase II, multicenter, open-label, single-arm study evaluating nivolumab in patients with locally determined dMMR or MSI-H metastatic colorectal cancer whose disease had progressed during, after, or were intolerant to, prior treatment with fluoropyrimidine-, oxaliplatin-, or irinotecan-based chemotherapy. In this study, 74 patients received nivolumab 3 mg/kg administered intravenously every 2 weeks. The recommended dose is 240 mg administered as an intravenous infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity. Across the 74 patients, 72% received prior treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. Efficacy outcome measures included independent radiographic review committee–assessed confirmed overall response rate per RECIST 1.1, and duration of response. More than half of patients (51%) had a BRAF (16%) or KRAS (35%) mutation.

In this trial, nivolumab demonstrated an overall response rate of 28% (95% confidence interval [CI] = 17–42; 15/53) in patients who received prior treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, including a 1.9% complete response rate (1/53) and a 26% partial response rate (14/53). Median duration of response in these patients was not reached(range, 2.8+ to 22.1+ months). Among all enrolled patients, 32% (95% CI = 22–44; 24/74) responded to treatment with nivolumab, including a 2.7% complete response rate (2/74) and a 30% partial response rate (22/74). The median duration of response was not reached (range, 1.4+ to 26.5+ months).

Data from CheckMate 142 were published by Overman et al in The Lancet Oncology in July.

Select Safety Profile

The most common adverse reactions (≥ 20%) in patients who received nivolumab as a single agent were fatigue; rash; musculoskeletal pain; pruritus; diarrhea; nausea; asthenia; cough; dyspnea; constipation; decreased appetite; back pain; arthralgia; upper respiratory tract infection; and pyrexia.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend universal MMR or MSI testing for all patients with a personal history of colon or rectal cancer to inform use of immunotherapy in patients with metastatic disease. The National Comprehensive Cancer Network® (NCCN®) panel recommends nivolumab as a category 2A treatment option in patients with metastatic deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) colorectal cancer in second- or third-line therapy.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.