Keytruda Approved for Early Treatment of Colorectal Cancer in Patients With Genetic Mutations

Merck's checkpoint inhibitor Keytruda (pembrolizumab) has been approved for patients with hard-to-treat colorectal cancer if they have genetic mutations already known to respond well to the drug.

Monday’s FDA approval is based on results presented a month ago at the annual meeting of the American Society of Clinical Oncology, which was held online. Scientists at ASCO said Keytruda, which cut the risk of death or cancer progressing by 40% compared with chemotherapy, would quickly become the new standard of care in certain patients.

Merck announced Keytruda's approval for use as a first-line, single-agent therapy in patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) mutations, who account for about 5% of metastatic colorectal cancer patients. Keytruda’s effectiveness when this mutation is present is well-recognized, and led to FDA’s first tissue-agnostic approval in May 2017. Merck received a second biomarker-based approval for pediatric patients with these mutations last month.

FDA’s action is based on results from KEYNOTE-177, a phase 3 trial of 307 patients, which found that Keytruda doubled progression-free survival from 8.2 months to 16.5 months.

At ASCO, lead study author Thierry André MD, of the Sorbonne Université and Hôpital Saint Antoine in Paris, said the findings would change the standard of care and that the results showed the value of biomarker-driven studies. Michael Overman, MD, of The University of Texas MD Anderson Cancer Center, a commentator at ASCO, said that going forward it would be “critical” to test every colorectal patient for the MSI-H/ dMMR mutations.

In its statement, Merck officials said the approval was handled under Project Orbis, an FDA initiative that allows for collaboration and a single submission with multiple international agencies; the new indication was also reviewed by regulators in Australia, Canada, and Switzerland.

“Today’s approval has the potential to change the treatment paradigm for the first-line treatment of patients with MSI-H colorectal cancer, based on the important findings from KEYNOTE-177 that showed Keytruda monotherapy demonstrated superior progression-free survival compared to standard of care chemotherapy,” Roy Baynes, MD, PhD, senior vice president and head of global clinical development, chief medical officer for Merck Research Laboratories, said in the statement.