The decision comes almost exactly a month after results from KEYNOTE-177 were presented at ASCO.
Merck, which makes pembrolizumab, sold as Keytruda, announced the approval in a statement.
The approval covers patients who have microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer and is based on results of KEYNOTE-177, a phase 3 trial of 307 patients that found the programmed cell death-1 (PD-1) inhibitor trimmed the risk of death of disease progression 40% compared with chemotherapy, which is the current standard of care (HR= 0.60, 95% CI: 0.45-0.80, P = .0004).
Results presented at ASCO showed that pembrolizumab doubled progression-free survival in these colorectal cancer patients, from 8.2 months to 16.5 months. Lead study author Thierry André MD, of the Sorbonne Université and Hôpital Saint Antoine in Paris, said at the time that the findings would change the standard of care. “No medical treatment has shown such an improvement,” André said.
Discussant Michael Overman, MD, of The University of Texas MD Anderson Cancer Center, agreed, and said the tumors treated in the study were particularly good candidates for immunotherapy. From now on, he said, “It is critical that we test all colorectal cancer patients for mismatch repair or microsatellite status.”
The approval came less than a month after Merck submitted a supplemental Biologics License Application (sBLA), which was handled through FDA’s Real-Time Oncology Review (RTOR) pilot program. According to the Merck statement, the approval was reviewed under Project Orbis, an initiative of the FDA Oncology Center of Excellence that allows for concurrent submission and review of oncology drugs among its international partners—in this case, 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.
At ASCO, André trumpeted the value of biomarker-driven research, and Baynes did the same today. “Our commitment to pursuing biomarker research continues to help us bring new treatments to patients,” he said, “particularly for those who have few available options.”
Immune-related adverse reactions can include pneumonitis, colitis, hepatitis, skin reactions, renal dysfunction and endocrinological abnormalities. Patients taking the PD-1 inhibitor may experience solid organ transplant rejection or complications from stem cell transplant.
Luis A. Diaz, MD, head of the division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center said in the statement that patients with colorectal cancer and the genetic mutations in the study have “historically faced poor outcomes, and until today, chemotherapy-containing regimens were the only FDA-approved first-line treatment options.”
About 5% of metastatic colorectal cancer patients have MSI-H/dMMR. Pembrolizumab’s effectiveness when this mutation is present is well-recognized, and led to FDA’s first tissue-agnostic approval in May 2017.