FDA Approves Opdivo for Additional Indication in Colon Cancer

Bristol-Myers Squibb (BMS) announced today that the FDA approved nivolumab (Opdivo) for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer that has progressed after treatment with fluoropyrimidine, oxaliplatin, and irinotecan, according to a press release.

The new indication received accelerated approval based on overall response rate (ORR) and duration of response; however, continued approval may be dependent on clinical benefit observed in further trials.

For patients with MSI-H or dMMR metastatic colorectal cancer, the recommended dose of nivolumab is 240-mg infused over 1 hour every 2 weeks until progression or toxicity, according to BMS.

“As part of our commitment to address hard-to-treat cancers, with today’s approval, Opdivo provides a new treatment option for these patients who have historically faced a poor prognosis,” said Chris Boerner, president, US Commercial at BMS. “This approval is one example of how our commitment to translational medicine and investigating predictive biomarkers may help us discover treatment approaches to address different patients’ unique needs.”

The approval was based on positive findings from the CheckMate-142 clinical trial, which included 74 treatment-experienced patients with MSI-H or dMMR colorectal cancer. BMS noted that 51% of patients had a BRAF or KRAS mutation. Efficacy outcome measures included confirmed ORR and duration of response.

The investigators found that nivolumab had an ORR of 28% in patients who received prior treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, according to the release. While 1 patient achieved a complete response, 14 achieved a partial response.

Among all patients included in the trial, 32% responded, with 2 achieving a complete response and 22 achieving a partial response.

“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.”

BMS warns that treatment with nivolumab may result in immune-mediated conditions, such as pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, skin reactions, encephalitis, infusion reactions, and embryo-fetal toxicity, according to the release.

Other common adverse reactions include fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, upper respiratory tract infection, and pyrexia, according to the release.

“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.8 The approval of Opdivo for appropriate patients with this disease gives the community more hope,” said Michael Sapienza, chief executive officer of the Colon Cancer Alliance.