Drug Is First to Treat Cancer Based on Genetics, Not Location

In a first for precision medicine, a cancer drug has won regulatory approval based on the genetic characteristic of tumors, rather than their location in the body.

On May 23, the U.S. Food and Drug Administration said it had approved Keytruda, an immunotherapy, for patients who have genetic glitches in so-called “mismatch repair” genes.

Mutations in these genes mean their cells don’t fully repair errors in DNA. That can trigger cancer, but it also makes their tumors particularly susceptible to drugs like Keytruda, which is marketed by Merck.

In a statement, Richard Pazdur, acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, called the approval “an important first for the cancer community.”

Precision medicine is the idea that medical treatments should be personalized to an individual’s genetic makeup, or other information about them. But up until now, cancer therapies have all been approved to treat cancer based on where it is located, such as in the breast or lung.

Keytruda is the first that can be given to anyone who harbors one of two relatively rare genetic abnormalities, and is suffering from a solid tumor, such as pancreatic or lung cancer. Olivier Lesueur, managing partner at Bionest Partners, a consulting firm, calls the approval a “breakthrough in the way we see and define cancer.”

Keytruda works by unleashing the body’s immune system to attack tumors, and was first approved to treat advanced skin cancer in 2014. Such drugs, called checkpoint inhibitors, have had remarkable success, including saving the life of former U.S. President Jimmy Carter. The downside of immunotherapy is that not all patients seem to benefit, for reasons that remain uncertain.

With the new approval, the number of patients expected to benefit could grow substantially. About 4 percent of all advanced cancers—up to 30,000 patients a year in the U.S.—harbor the genetic abnormalities that Keytruda can treat, says Dung Le, oncologist at the Johns Hopkins Bloomberg-Kimmel Institute for Immunotherapy.

“This drug is going to reach patients we would not have offered the therapy to before,” says Le.

The new approval only applies to patients for whom traditional treatment, like chemotherapy, has already failed. But genetic tests to identify patients with mismatch repair genes are widely available and cost $300 to $600, says Le. Keytruda itself costs around $150,000 a year.

Merck won a so-called “accelerated” approval based on a clinical trial involving just 149 patients with 15 different types of cancers at Johns Hopkins and four other hospitals. In the trial, about 40 percent of patients experienced complete or partial shrinkage of their tumors.

One of those patients is Adrienne Skinner, 60, of Larchmont, New York, who endured surgery and a year of chemotherapy after being diagnosed in 2013 with advanced ampullary cancer, a rare and deadly gastrointestinal cancer.

In April 2014, Skinner joined the Keytruda study. She was a candidate because she was born with Lynch syndrome, an inherited condition in which her DNA repair genes don’t work correctly. After just a few months on the drug, a surgeon examined her and told Skinner her tumor had disappeared.

Skinner continued on the drug for another two years and says she now feels like her normal self again. She works full-time, goes to the gym most days, plays tennis, and does yoga. If not for the drug, she says, “I’d be dead by now.”