Tumor-gene testing urged to tell whether drug targets your cancer

WASHINGTON -- Colon cancer. Uterine cancer. Pancreatic cancer. Whatever the tumor, the more gene mutations lurking inside, the better chance your immune system has to fight back.

That's the premise behind the recent approval of a landmark drug, the first cancer therapy ever cleared based on a tumor's genetics instead of the body part it struck first. Now thousands of patients with worsening cancer despite standard treatment can try this immunotherapy -- as long as genetic testing of the tumor shows they're candidates.

"It's like having a lottery ticket," said Johns Hopkins oncologist Dr. Dung Le, who helped prove the new use for the immunotherapy Keytruda. "We've got to figure out how to find these patients, because it's such a great opportunity for them."

Today, doctors diagnose tumors by where they originate -- breast cancer in the breast, colon cancer in the colon -- and use therapies specifically tested for that organ. In contrast, the Food and Drug Administration labeled Keytruda the first "tissue-agnostic" treatment, for adults and children.

The reason: Seemingly unrelated cancers occasionally carry a common genetic flaw called a mismatch-repair defect. Despite small studies, the FDA found the evidence convincing that for a subset of patients, that flaw can make solid tumors susceptible to immunotherapy doctors otherwise wouldn't have tried.

"We thought these would be the hardest tumors to treat. But it's like an Achilles heel," Hopkins cancer geneticist Bert Vogelstein said.

And last month, FDA Commissioner Scott Gottlieb told a Senate subcommittee his agency will simplify drug development for diseases that "all have a similar genetic fingerprint, even if they have a slightly different clinical expression."

Hopkins estimates about 4 percent of cancers are mismatch-repair deficient, potentially adding up to 60,000 patients a year. Widely available tests that cost $300 to $600 can tell who's eligible.

The FDA said the flaw is more common in colon, endometrial and gastrointestinal cancers but occasionally occurs in a list of others.

Most tumors bear 50 or so mutations in various genes, Vogelstein said. Melanomas and lung cancers, spurred by sunlight and tobacco smoke, may have twice as many. But tumors with a mismatch-repair defect can harbor 1,500 mutations.

Why? When DNA copies itself, sometimes the strands pair up wrong to leave a typo -- a mismatch. Normally the body spell-checks and repairs those typos. Without that proofreading, mutations build up.