FDA Approves Frontline Pembrolizumab for MSI-H/dMMR CRC

The FDA approved pembrolizumab for IV injection for the first-line treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer.

The FDA has approved pembrolizumab (Keytruda) for intravenous (IV) injection for the first-line treatment of patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer.

Pembrolizumab is now the first immunotherapy approved for this patient population as a first-line treatment which can be administered to patients without also giving chemotherapy.

“Metastatic colorectal cancer is a serious and life-threatening disease with a poor prognosis. Available current therapy with chemotherapy combinations and other biologics are associated with substantial toxicity,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a press release. “Having a non-chemotherapy option available for selected patients is a noteworthy paradigm shift in treatment.”

The approval for this indication was based on results from a multicenter, international, open-label, active-controlled, randomized trial that compared pembrolizumab with chemotherapy treatment in 307 patients with MSI-H or dMMR metastatic colorectal cancer.

The study demonstrated a statistically significant improvement in progression-free survival (PFS) as assessed by blinded independent review. Median PFS was 16.5 months in the Keytruda group and 8.2 months in the standard of care group. However, longer-term analysis is still needed to assess for an effect on survival.

Common adverse events (AEs) observed with pembrolizumab include fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain. Pembrolizumab has also been known to cause immune-mediated AEs, including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis.

Per the FDA’s recommendation, patients who experience severe or life-threatening infusion-related reactions should stop taking pembrolizumab. Moreover, women who are pregnant should be advised that pembrolizumab may cause harm to a developing fetus. Women who are breastfeeding should also not take pembrolizumab, as it may cause harm to a breastfed child.


FDA. FDA Approves First-Line Immunotherapy for Patients with MSI-H/dMMR Metastatic Colorectal Cancer. FDA website. Published June 29, 2020. fda.gov/news-events/press-announcements/fda-approves-first-line-immunotherapy-patients-msi-hdmmr-metastatic-colorectal-cancer. Accessed June 29, 2020.