FDA’s Keytruda Approval for Subset of Advanced Endometrial Cancer Provides Patients With a ‘Practice Changing’ Treatment Option

The Food and Drug Administration’s (FDA) recent approval of Keytruda (pembrolizumab) for patients with advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, provides patients with a personalized treatment option.

Keytruda, an anti-PD-1 therapy, is now also indicated for patients with disease progression after systemic therapy who are not candidates for radiation or curative surgery.

“This gives our patients an option well beyond what is available with historical treatments for recurrent and progressive endometrial cancer. It also allows us to personalize those approaches to look at those patients who are deficient in (mismatch repair) and looking at identifying those patients who are going to benefit the most,” said Dr. David M. O’Malley, the division director and professor in the Division of Gynecologic Oncology at The Ohio State University Wexner Medical Center in Columbus and The James Comprehensive Cancer Center in Columbus.

Prior to immunotherapies such as Keytruda, treatment options for patients with advanced endometrial cancer were limited with modest response rates as low as 10% to 15%, he said.

“The full approval absolutely fills a high unmet need. We really don’t have any agents that are approved for endometrial cancer. We have agents which we commonly use, but beyond hormonal therapy, the options for these patients are very limited,” O’Malley said in an interview with CURE®.

The FDA approval of Keytruda was based on results of the KEYNOTE-158 trial. During a median follow-up of 16 months, patients who were treated with Keytruda had an objective response rate (a measure of response to treatment) of 46%. Additionally, there was a complete response rate (the disappearance of all cancer from treatment, although this doesn’t mean it has been cured) of 12% and partial response rate (decrease in tumor size or extent of cancer in the body from treatment) of 33%.

“These results are really practice changing,” he said. “The meaning (for) patients is that we have a well-tolerated, convenient treatment with a potential as high as nearly 15% of a complete response. And again, to reemphasize, (there is) potentially the option of getting rid of their cancer so it doesn’t come back in a group of these endometrial cancer patients.”

Out of the 41 patients who responded to Keytruda in the trial, 68% continued to have a response for at least 12 months and 44% had a response that lasted at least 24 months. The median duration of response (the time a tumor continues to respond to treatment without growth or spread) was not reached — a result meaning that patients were continuing to respond to treatment when it was assessed by researchers.

“We may be talking about options for curative intent in women with recurrent endometrial cancer, something which I didn’t think I’d see in my lifetime,” O’Malley added.

The most common side effects, occurring in at least 20% of patients, included fatigue, musculoskeletal pain, rash, diarrhea, fever, cough, decreased appetite, itching, shortness of breath, constipation, pain, abdominal pain, nausea and hyperthyroidism.

There are also immune-related side effects associated with Keytruda which include pneumonitis (lung tissue inflammation), colitis (inflammation of the inner lining of the colon), hepatitis, endocrinopathies (conditions related to the endocrine gland such as hypothyroidism and hyperthyroidism), nephritis (inflammation of nephrons in the kidneys) and skin reactions.

“The good news is mostly these (side effects) are mild and well managed,” O’Malley explained. “But it does force us to look beyond our normal chemotherapy-associated side effects of low counts, fatigue or neuropathy. It really allows us, or forces us, to be cognizant of all immune-associated toxicity, which takes an entire team to be aware of these immune-associated toxicities. This means a patient’s entire multidisciplinary team, including oncologists, nurses and nurse practitioners, should be aware of these toxicities that can occur and may have an effect on a patient’s immune system, he said.

“I think this approval is more than significant. I think this approval is practice changing to allow for our patients the access to a well-tolerated regimen with such a high response rate and most importantly the duration of the responses when they do occur.”

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