The immune checkpoint inhibitor nivolumab has shown durable responses and disease control in pretreated patients with DNA mismatch repair deficient/microsatellite instability high (MSI-H) metastatic colorectal cancer, according to a presentation at the Gastrointestinal Cancers Symposium.
Approximately 4% of all patients with metastatic colorectal cancer have MSI-H, indicating a deficient DNA mismatch repair system. These patients tend to be less responsive to conventional chemotherapy and exhibit higher levels of tumor neoantigens, tumor-infiltrating lymphocytes, and expression of checkpoint regulators in immune cells. A common belief is that patients with DNA mismatch repair deficient MSI-H metastatic colorectal cancer may be targetable by immune checkpoint inhibitors.
Researchers led by Michael J Overman, MD, University of Texas MD Anderson Cancer Center, conducted a study to test response of the immune checkpoint inhibitor nivolumab in heavily pretreated patients with DNA mismatch repair deficient MSI-H metastatic colorectal cancer. Researchers enrolled 74 patients, 84% of whom had received two or more prior lines of therapy and had progressed. Patients were assigned to received nivolumab (3 mg/kg) every 2 weeks until the primary endpoint, overall response rate per investigator assessment, was reached. Secondary endpoints included overall response rate by blinded independent review.
Results of the study showed the overall response rate was 31.1% per investigator and 27% by review committee after a median follow-up of 7.4 months. No complete responses were reported by investigators, but there were 23 partial responses and 29 patients showed stable disease (disease control rate for 12 or more weeks, 68.9%). Two complete responses were reported by the blinded independent review, along with 18 partial responses and 29 patient cases of stable disease (disease control rate for 12 or more weeks, 62.2%). Median progression-free survival (PFS) was 9.6 months with a 12-month rate of 48.4% per investigator review.
Grade III-IV treatment-related adverse events were reported in 20.3% of patients, including acute kidney injury, increased alanine aminotransferase, colitis, and stomatitis. There were no deaths related to drug toxicity in the study.
Researchers concluded that nivolumab showed durable responses and disease control, deeming it an acceptable treatment option for MSI-H metastatic colorectal cancer.
“These results suggest that nivolumab should be considered a new standard of care for patients with previously treated MSI-H advanced CRC,” said Dr Overman. “This is in line with the recent amendment to NCCN guidelines which recommend all metastatic colorectal cancer patients have testing for MSI-H and also patients with MSI-H colorectal cancer after initial therapy be considered for either pembrolizumab or nivolumab monotherapy.”