For Immediate Release:


Today, the U.S. Food and Drug Administration approved Keytruda (pembrolizumab) for intravenous injection for the first-line treatment of patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer. This marks the first immunotherapy approved for this patient population as a first-line treatment and which is administered to patients without also giving chemotherapy.

MSI-H and dMMR tumors contain abnormalities that affect the proper repair of DNA inside the cell. The frequency of MSI-H varies across tumor types and stages, and approximately 5% of patients with metastatic colorectal cancer have MSI-H or dMMR tumors.

“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,” said Richard Pazdur, M.D., 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. “Having a non-chemotherapy option available for selected patients is a noteworthy paradigm shift in treatment.”

Keytruda works by targeting the cellular pathway of proteins found on the body’s immune cells and some cancer cells, known as PD-1/PD-L1. By blocking this pathway, Keytruda may help the body’s immune system fight the cancer cells and provide a benefit in patients with MSI-H or dMMR metastatic colorectal cancer. The FDA previously approved Keytruda to treat other types of cancer.

The FDA’s approval for this indication was based on the results of one multicenter, international, open-label, active-controlled, randomized trial that compared Keytruda 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. Longer-term analysis is needed to assess for an effect on survival.

Common side effects of Keytruda include fatigue, musculoskeletal pain, decreased appetite, itchy skin (pruritus), diarrhea, nausea, rash, fever (pyrexia), cough, difficulty breathing (dyspnea), constipation, pain, and abdominal pain. Keytruda can cause serious conditions known as immune-mediated side effects, including inflammation of healthy organs such as the lungs (pneumonitis), colon (colitis), liver (hepatitis), endocrine glands (endocrinopathies) and kidneys (nephritis). Patients who experience severe or life-threatening infusion-related reactions should stop taking Keytruda. Women who are pregnant should be advised that Keytruda may cause harm to a developing fetus. Women who are breastfeeding should not take Keytruda because it may cause harm to a breastfed child.

The FDA granted this application Priority Review, which directs overall attention and resources to the evaluation of applications for drugs that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications. This review also used the Real-Time Oncology Review, which streamlines data submission prior to the filing of the entire marketing application, the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment of an application, and Summary Level Review, which allows FDA to rely on qualified data summaries to support approval of a supplemental application. The FDA collaborated with international agency counterparts on the review of this application as part of Project Orbis.

The FDA granted this approval of Keytruda to Merck & Co.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.



Related Information