The FDA just approved a drug that targets cancer by genetic marker, not body parts

A first for cancer research and Merck.
A first for cancer research and Merck.
Image: Reuters/Jeff Zelevansk
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Cancer care is changing. Someday soon doctors may not be so concerned with whether the disease originates in the colon, lungs, or breast. Instead of categorizing cancers by body parts, they’ll use biomarkers like MSI-H or dMMR to identify and treat the illness.

On May 23, the US Food and Drug Administration (FDA) granted accelerated approval to pembrolizumab, made by Merck and marketed as Keytruda, for adults and children without remaining treatment alternatives and with metastatic solid tumors identified with a biomarker called microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR).

Tumors with MSI-H and dMMR markers—most commonly found in colorectal, endometrial, and gastrointestinal cancers—have abnormalities that affect DNA repair inside the cell. It’s believed that Keytruda works by blocking a cellular pathway known as PD-1/PD-L1, containing proteins found on the body’s immune cells and some cancer cells. The drug “may help the body’s immune system fight the cancer cells” but the FDA doesn’t specify how.

In clinical trials, pembrolizumab showed promise treating cancers originating in 15 different locations. The FDA decision is based on a study of 90 patients with colorectal cancer and 59 patients diagnosed with one of 14 other cancer types. Of these 149 patients, 39% had a complete or partial shrinkage of tumors, which for 78% of patients lasted for six months or more.

It’s not perfect, and more research has to be done, but the approval is a landmark because it’s the first time a cancer treatment that is not site- or tissue-specific has received the agency’s approval. (The drug had already been approved for certain specific cancer treatments—metastatic melanoma, metastatic non-small cell lung cancer, recurrent or metastatic head and neck cancer, refractory classical Hodgkin lymphoma, and urothelial carcinoma.)

“This is an important first for the cancer community,” said Richard Pazdur, of the FDA’s Center for Drug Evaluation and Research in a statement. “Until now, the FDA has approved cancer treatments based on where in the body the cancer started—for example, lung or breast cancers. We have now approved a drug based on a tumor’s biomarker without regard to the tumor’s original location.”

The approval is an old dream come true for some cancer researchers. Gates Foundation CEO Sue Desmond-Hellman, formerly chief cancer drug developer at Genentech and a pioneer in the field of gene-targeted cancer drugs, said as much on Twitter upon hearing the news.

It’s also great news for the drug maker Merck, and it came at the perfect time; earlier the same day, the UK’s Competition and Markets Authority accused the US-based pharma company of “offering unfair discounts” on infliximab, its blockbuster rheumatoid arthritis and Crohn’s disease drug, to “discourage new competitors,” according to the Financial Times.

Next month, Merck will present the findings of 50 studies testing pembrolizumab’s use on 16 different cancers at the 53rd Annual Meeting of the American Society of Clinical Oncology.

But much remains to be done. The FDA expects Merck to conduct more testing on pembrolizumab’s efficacy for cancer treatment according to genetic markers. Accelerated approval for experimental drugs is only granted where there is an unmet medical need for a serious condition; in this case “serious condition” includes multiple cancers now classified by two genetic markers.

The drug was shown to have “certain effects that are reasonably likely to predict a clinical benefit to patients,” according to the FDA. That’s not quite a ringing endorsement—it’s more like a muted grant of permission to keep working on it and come back soon. In the agency’s words, “Further study is required to verify and describe anticipated clinical benefits of Keytruda, and the sponsor is currently conducting these studies in additional patients with MSI-H or dMMR tumors.”