Keytruda Has Received Nearly 40 FDA Approvals. How Does It Work?

An expert explains how immunotherapy works.

The Food and Drug Administration (FDA) recently approved Keytruda (pembrolizumab) plus chemoradiotherapy (CRT) for the treatment of patients with stages 3 to 4A cervical cancer. The first approval of an anti-programmed death receptor-1 (PD-1) therapy in combination with chemoradiotherapy for this patient population, this was the third FDA approval for the treatment of cervical cancer with Keytruda and the 39th indication for Keytruda in the United States, according to a news release from Merck, the manufacturer of the drug.

CURE® spoke with Dr. Linda R. Duska, a gynecologic oncologist at University of Virginia Health and the United States principal investigator on KEYNOTE-A18, the study which served as the basis of the recent FDA approval, about why Keytruda has proven to be such an effective cancer treatment, particularly when administered in concert with chemoradiotherapy.

“We think that it works by turning the immune system on and improving the immune response to the tumor, not just in the tumor but also in the tumor microenvironment, so (meaning) the space in your body where the tumor lives,” Duska said. “So, if you have a tumor where maybe (Keytruda) doesn't work so well but then you mix the pembrolizumab with radiation, maybe the radiation releases something in the tumor that makes the (Keytruda) work better. ... We don't know (for sure), but that's a theory.”

There is a study currently underway, Duska said, to determine if Keytruda has to be given during chemoradiation treatment, or if it can be given to patients as a maintenance therapy.

“We don't know the answer to that question, but we're going to,” Duska said.

At least 10% of the patients who participated in KEYNOTE-A18 and were treated with Keytruda and chemoradiotherapy experienced side effects included nausea, diarrhea, vomiting, urinary tract infection, fatigue, hypothyroidism, constipation, decreased appetite, weight loss, abdominal pain, pyrexia (fever), hyperthyroidism, dysuria (painful urination), rash and pelvic pain, according to the FDA.

“These immunotherapies, not just (Keytruda), but all of them, we call them checkpoint inhibitors (and) what they do is they turn the immune system on,” said Duska. “And that's why (with) the side effects that we see most often, I tell my patients (they) are -itises, like thyroiditis, or colitis or pneumonitis. We're turning the body's immune system on, not just against the tumor, but also globally against the body, really. And so that's why we see that side effect profile. But cervical cancer is caused by a virus, it's caused by the human papilloma virus, and so it almost makes intuitive sense that a virally driven tumor would respond to immunotherapy.”

Keytruda received its first approval from the FDA, for the treatment of some patients with melanoma, a decade ago in 2014. Since then, its nearly 40 approvals have been for patients with diseases including some non-small cell lung, head and neck, urothelial, colorectal, gastric and esophageal cancers.

Keytruda has also been approved, in combination with chemotherapy, for patients with persistent, recurrent, or metastatic cervical cancer and as a single agent for patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1, according to Merck.

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