Keytruda (pembrolizumab) has been approved by the FDA for treatment of cancers with a specific biomarker. It’s the first time the FDA has approved a cancer treatment based on a tumor’s genetic features rather than the location in the body where it originated.
“This is an important first for the cancer community,” said Richard Pazdur, M.D., acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research and director of the FDA’s Oncology Center of Excellence. “Until now, the FDA has approved cancer treatments based on where in the body the cancer started—for example, lung or breast cancers. We have now approved a drug based on a tumor’s biomarker without regard to the tumor’s original location.”
A recent Washington Post story tells how Keytruda, while still in clinical trials, reversed the progression of colon cancer in a 23-year-old woman whose oncologist had said was out of options. The woman’s younger sister found the clinical trial then underway at Johns Hopkins in Baltimore and a few years later, Stefanie Joho is in remission and free of any traces of cancer.
Cancer immunotherapy is also credited with the stunning recovery of former President Jimmy Carter, who had been suffering from brain cancer but is now in remission and cancer-free.
Keytruda, from Merck & Co., is indicated for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors that have been identified as having a biomarker referred to as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). This indication covers patients with solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options and patients with colorectal cancer that has progressed following treatment with certain chemotherapy drugs.
MSI-H and dMMR tumors contain abnormalities that affect the proper repair of DNA inside the cell. Tumors with these biomarkers are most commonly found in colorectal, endometrial and gastrointestinal cancers, but also less commonly appear in cancers arising in the breast, prostate, bladder, thyroid gland and other places. Approximately 5 percent of patients with metastatic colorectal cancer have MSI-H or dMMR tumors.
Keytruda works by targeting cellular pathways, helping the body’s immune system fight the cancer cells. The FDA previously approved Keytruda for the treatment of certain patients with metastatic melanoma, metastatic non-small cell lung cancer, recurrent or metastatic head and neck cancer, refractory classical Hodgkin lymphoma, and urothelial carcinoma.
“The FDA’s approval of this new indication for Keytruda further supports Merck’s commitment to helping people with difficult-to-treat cancers,” said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. “We are thankful to the researchers, as well as the patients and their families who helped make today’s approval possible.”
Keytruda was approved for this new indication using the Accelerated Approval pathway, under which the FDA may approve drugs for serious conditions where there is unmet medical need and a drug is shown to have certain effects that are reasonably likely to predict a clinical benefit to patients. Additional studies are underway.
The safety and efficacy of Keytruda for this indication were studied in patients with MSI-H or dMMR solid tumors enrolled in one of five uncontrolled, single-arm clinical trials.
Common side effects of Keytruda include fatigue, itchy skin (pruritus), diarrhea, decreased appetite, rash, fever (pyrexia), cough, difficulty breathing (dyspnea), musculoskeletal pain, constipation and nausea.
The recommended dose of Keytruda in adults is 200 mg administered as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. In children, the recommended dose of Keytruda is 2 mg/kg (up to a maximum of 200 mg) administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.