FDA Approves First-Ever, Pan-Cancer Drug in Milestone for Personalized Medicine

In what is being heralded a major milestone for personalized medicine, in late May the U.S. Food and Drug Administration (FDA) approved the first pan-cancer drug. This is the first-ever approval of a cancer drug based entirely on genomic alterations, regardless of tumor location.

The drug, Keytruda (Merck & Co.) is approved for treating for adult and pediatric patients with nonoperable or metastatic solid tumors identified as having microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) genetic alterations. This type of tumor most frequently occurs in colorectal, endometrial, and gastrointestinal cancers. Experts say that approximately four percent of advanced cancers (15,000 to 20,000 cases each year in the United States) carry these genetic alterations.

“This is the first time in the history of oncology that a cancer medicine has been approved by the FDA using a pan-tumor predictive biomarker rather than a tumor-specific approach,” said Luis A. Diaz, Jr., M.D., from Memorial Sloan Kettering Cancer Center, in a statement. “This approval for Keytruda is a transformational milestone in our progress toward personalized immunotherapy.”

Approval of the drug was based on 149 patients with MSI-H or dMMR cancers, identified across five separate clinical trials. A total of 15 cancer types were identified among the 149 enrolled patients. As with other targeted therapies, molecular testing is necessary to identify tumors carrying the necessary genetic marker.  The majority of patients had tumor status identified prospectively  (135 of 149) using local laboratory-developed, polymerase chain reaction (PCR) tests for MSI-H status or immunohistochemistry (IHC) tests for dMMR.

“When you take all of the cancers across the board, it’s probably 75 percent to 80 percent of cancers that should be tested,” said Drew Pardoll, M.D., Ph.D., from Johns Hopkins University and a collaborator of the Phase 2 trial testing of Keytruda, in a statement. “But any cancer for which there is no accepted therapy that will give any benefit should be tested if they’re one of those cancers.”