Other Agents

No prospective pediatric clinical trials have been conducted using checkpoint inhibitors. However, the U.S. Food and Drug Administration has granted accelerated approval to nivolumab for patients aged 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient metastatic colorectal cancer that has progressed following treatment with combination fluoropyrimidine, oxaliplatin, and irinotecan. This approval was based on extrapolation of the results of the CheckMate 142 trial. The trial showed an objective response rate of 31% and a disease control rate of 69% in patients with MSI-H or mismatch repair deficient colorectal cancers that had progressed after a regimen of fluoropyrimidine, oxaliplatin, and irinotecan.[8]

Pembrolizumab has also been approved for adult and pediatric patients with unresectable or metastatic MSI-H or mismatch repair deficient cancer, including colorectal cancer that has progressed after fluoropyrimidine, oxaliplatin, and irinotecan therapy. This approval was based on the KEYNOTE-164 trial, which demonstrated an objective response rate of 33% in patients with MSI-H or mismatch repair deficient metastatic colorectal cancer.[9] The approval was also based on the results of the KEYNOTE-117 trial, which included 307 treatment-naive patients with MSI-H or mismatch repair deficient colorectal cancer who were randomly assigned to receive pembrolizumab or a 5-FU–containing regimen. The trial showed that pembrolizumab was superior to chemotherapy, with respect to progression-free survival (median, 16.5 vs. 8.2 months; hazard ratio, 0.60; 95% confidence interval, 0.45–0.80; P = .0002).[10]

Other active agents used in adults include oxaliplatin, bevacizumab, panitumumab, cetuximab, aflibercept, and regorafenib.[11-14]