The US Food and Drug Administration (FDA) has approved another indication for nivolumab (Opdivo, Bristol-Myers Squibb Company). Nivolumab can now be used for the treatment of adult and pediatric patients (12 years and older) with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer that has progressed after treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.
Nivolumab, a programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, has already been approved for use in the United States for six other indications (melanoma, non–small cell lung cancer, bladder cancer, kidney cancer, squamous cell cancer of the head and neck, Hodgkin’s lymphoma, and urothelial carcinoma).
The new indication was granted under accelerated approval, which was based on overall response rate and duration of response. According to the FDA, continued approval for this indication may be contingent upon verification and description of clinical benefit in future confirmatory trials.
“Patients with metastatic colorectal cancer who have dMMR or MSI-H tumors are less likely to respond to conventional chemotherapy,” commented Heinz-Josef Lenz, MD, FACP, J. Terrence Lanni Chair in Gastrointestinal Cancer Research, University of Southern California, Los Angeles, in a statement. “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,” Dr Lenz added.
The FDA based its approval on the results of the CheckMate-142 study, a phase 2, multicenter, open-label, single-arm clinical trial that evaluated nivolumab in 74 patients with locally determined dMMR or MSI-H metastatic colorectal cancer. The patients all experienced disease progression during or after standard chemotherapy, or were intolerant of the regimen (fluoropyrimidine-, oxaliplatin-, or irinotecan-based chemotherapy).
The cohort received nivolumab at a dose of 3 mg/kg administered intravenously every 2 weeks, and 51% of the patients had a BRAF (16%) or KRAS (35%) mutation.
The overall response rate was 28% (95% confidence interval [CI]: 17-42; 15/53) following nivolumab treatment in patients who had been previously treated with a fluoropyrimidine, oxaliplatin, and irinotecan. In addition, 1.9% achieved a complete response (1/53), and a 26% achieved a partial response (14/53).
The median duration of response in this group has not yet been reached (range: 2.8 ± 22.1+ months).
For the entire cohort, 32% (95% CI: 22 – 44; 24/74) experienced a response, including 2.7% who achieved a complete response (2/74) and 30% who achieved a partial response (22/74).
The median duration of response also has not been reached (range: 1.4 ± 26.5+ months).
The most common adverse reactions (≥20%) observed in this trial were fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, upper respiratory tract infection, and pyrexia.
The National Comprehensive Cancer Network (NCCN) panel recommends nivolumab as a category 2A treatment option for patients with dMMR or MSI-H colorectal cancer as second- or third-line therapy. The NCCN practice guidelines also recommend universal MMR or MSI testing for all patients with a personal history of colon or rectal cancer to inform the use of immunotherapy in metastatic disease.
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