The FDA has approved pembrolizumab (Keytruda, Merck) as a first-line treatment for unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer.

According to a press release, this is the first single-agent, anti-PD-1 therapy approved in the first-line environment for this patient population.

“Patients with unresectable or metastatic MSI-H colorectal cancer have historically faced poor outcomes, and until today, chemotherapy-containing regimens were the only FDA-approved first-line treatment options,” said Luis A. Diaz, MD, head of the division of Solid Tumor Oncology at Memorial Sloan Kettering Cancer Center, in a statement.

The approval was based on the phase 3 Keynote-177 trial, which found that pembrolizumab significantly reduced the risk of disease progression or death by 40% compared with chemotherapy. The study enrolled 307 patients who were randomized 1:1 to receive 200 mg of pembrolizumab intravenously every 3 weeks, or an investigator’s choice of 2 chemotherapy regimens given intravenously every 2 weeks.

Patients who received pembrolizumab also had a more than double median progression-free survival compared with patients who received the standard-of-care chemotherapy (16.5 months vs 8.2 months).

Among the 153 patients with MSI-H or dMMR colorectal cancer who received pembrolizumab, the median duration of exposure to pembrolizumab was 11.1 months. Adverse events (AEs) were similar to those observed in 2799 patients with melanoma or non-small cell lung cancer who were treated with pembrolizumab as a single agent.

Immune-related AEs can occur with the drug, including pneumonitis, colitis, hepatitis, and nephritis and renal dysfunction. It can also cause severe or life-threatening infusion-related reactions.

“In patients who were treated with Keytruda and responded in the Keynote-177 trial, 43% of patients experienced a duration of response lasting 2 years or longer,” Diaz said in the release. “This approval helps address the unmet need to provide a new monotherapy treatment option for patients.”

REFERENCE
FDA Approves Merck’s Keytruda (pembrolizumab) for First-Line Treatment of Patients With Unresectable or Metastatic MSI-H or dMMR Colorectal Cancer [news release]. Merck; June 29, 2020. https://www.mrknewsroom.com/newsroom/news-releases/news-details/2020/FDA-Approves-Mercks-KEYTRUDA-pembrolizumab-for-First-Line-Treatment-of-Patients-With-Unresectable-or-Metastatic-MSI-H-or-dMMR-Colorectal-Cancer/default.aspx. Accessed June 30, 2020.