FDA Clears Cancer Drug Keytruda Based on Genetics, Not Tumor Location

Approval marks major step in precision medicine

The FDA has approved a new indication for pembrolizumab (Keytruda, Merck), an anti-programmed death 1 (PD-1) receptor therapy. Pembrolizumab is now indicated for the treatment of adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair-deficient solid tumors that have progressed after prior treatment and who have no satisfactory alternative treatment options, or patients with colorectal cancer that has progressed after treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.

Pembrolizumab is the first cancer drug approved by the FDA based on a patient’s genetic traits, regardless of where in the body the disease originated. The approval marks a major step in so-called precision medicine, in which genetic biomarkers may determine the course of therapy rather than the type of cancer, according to Reuters.

The new indication was approved under accelerated approval based on the tumor response rate and the durability of response. Continued approval for this indication may be contingent on the verification and description of clinical benefit in confirmatory trials.

The safety and efficacy of pembrolizumab in pediatric patients with MSI-H central nervous system cancers have not been established.

Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Binding of the PD-1 ligands to the PD-1 receptor on T cells inhibits T-cell proliferation and cytokine production. By blocking the interaction of PD-1 with PD-L1 and PD-L2, pembrolizumab releases PD-1 pathway-mediated inhibition of the immune response, including the antitumor immune response.

The recommended dosage of pembrolizumab in adults is 200 mg administered as an intravenous (IV) infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity occur, or up to 24 months in patients without disease progression. In children, the recommended dosage of pembrolizumab is 2 mg/kg (up to a maximum of 200 mg) administered as an IV infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity occur, or up to 24 months in patients without disease progression.

Treatment with pembrolizumab has been associated with immune-mediated pneumonitis, including fatal cases; immune-mediated colitis; immune-mediated hepatitis; hypophysitis; thyroid disorders, including hyperthyroidism, hypothyroidism, and thyroiditis; type-1 diabetes mellitus, including diabetic ketoacidosis; and immune-mediated nephritis.

Pembrolizumab was previously approved to treat patients with advanced melanoma, advanced non–small-cell lung cancer, head-and-neck cancers, and classical Hodgkin’s lymphoma. Last week, pembrolizumab won U.S. approval for bladder cancer, and it is now awaiting an FDA decision for gastric cancer.

Sources: Merck; May 23, 2017; Reuters; May 23, 2017; and Keytruda Prescribing Information; May 2017.