FDA Landmark Nod: Cancer Drug To Match Tumor Genes, Not Tissue Type

Xconomy National — 

For many years, doctors and researchers have known that cancers in different parts of the body can share genetic abnormalities. For the first time, the FDA has approved a drug based on those abnormalities and not on the organ in which the cancer originated.

It’s a moment that a lot of people in the cancer field have been waiting for. The CEO of the Bill and Melinda Gates Foundation and former top Genentech official Susan Desmond-Hellman wrote on Twitter: “20 yrs ago at Genentech I gave a speech dreaming of a cancer clinic with doors saying ‘HER2, EGFR, ..’, not ‘Breast, Kidney,…’ Maybe now?” (HER2 and EGFR are well-known genetic alterations in various cancers.)

The approval is for pembrolizumab (Keytruda), which has already received approval in skin, lung, bladder, and other cancers.

The FDA now says pembrolizumab, from Kenilworth, NJ-based Merck (NYSE: MRK), can be used for children and adults whose advanced solid tumors have conditions known as microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR), and haven’t responded to prior treatment. MSI-H and dMMR tumors have lost the ability that cells normally use to repair their own DNA errors. Without that ability, cells with DNA errors can proliferate and turn into cancer.

“This is an important first for the cancer community,” said Richard Pazdur, the acting director of the FDA’s office of hematology and oncology products, in the agency’s announcement.

MSI-H and dMMR cells can be found in patients with several tumor types, including colorectal, endometrial, and stomach cancers. About 5 percent of patients with metastatic colorectal cancer, for example, have MSI-H or dMMR tumors, according to the FDA’s statement.

The FDA decision was based on five clinical trials enrolling 149 patients with MSI-H or dMMR solid tumors across 15 cancer types. Of the 149 patients, 39.6 percent had at least a partial response to treatment, meaning their tumors shrunk. The response lasted at least six months for 78 percent of those patients.

Drew Pardoll, the director of the Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy—where, it should be noted, the early research regarding these genetic insights originated—told Xconomy that patients with MSI-H or dMMR tumors tend to respond very poorly to chemotherapy.

Their luck has now changed, he says. Genetic testing is now available to identify these abnormalities, and people with these tumors tend to respond well to treatment with a so-called checkpoint inhibitor that blocks a protein called PD-1, like Merck’s pembrolizumab. “I predict that this is going to be the single most commonly done genetic test in oncology,” Pardoll said. “It’s going to be done all over the place.”

Johns Hopkins has filed for a patent for a companion diagnostic testing for MSI-H or dMMR tumors, and has licensed that technology to a company in Baltimore called Personal Genome Diagnostics. A Johns Hopkins spokesperson said the institution may thus stand to benefit, but it’s not clear to what extent since the test is already widely used and can be done by many companies and hospitals.

The approval could help push adoption of broad cancer genetic tests, which insurers have been slow to cover. The more evidence that tests are steering patients to better results from expensive therapies—and away from therapies that are not likely to benefit them—the more chance insurers will pay for those tests, said Dana-Farber Cancer Institute president and CEO Laurie Glimcher at an Xconomy forum last week. “It’s going to cost some money to do those kinds of tests,” said Glimcher. “But ultimately you’re not going to be putting patients on drugs that you can predict they will not respond to. I have to believe that the economics will eventually triumph.”

Cancer immunotherapies have produced stunning results in recent years, but they face significant limitations. Only a fraction of patients respond to drugs like pembrolizumab and Bristol-Myers Squibb’s nivolumab (Opdivo), and researchers are still trying to figure out why. Companies are combining these drugs with a variety of others hoping more patients will respond, and more cancers will be impacted. Many of these studies, however, will likely fail. Finding more biomarkers like MSI-H, and uncovering more genetic clues as to why two patients with the same type of cancer will have different results, could help increase the odds of success.

“I worry that [so many companies] race into phase 3 trials and there’s not enough biomarker work to understand why things work and why they don’t work,” Pardoll said.

The FDA’s decision was an “accelerated” approval, on a thinner body of evidence than is typically required. That means that the FDA can withdraw its approval if the drug fails to show the anticipated benefit in ongoing studies.