Keytruda Regimen Misses Goal in Endometrial Cancer Trial

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Adding Keytruda to chemotherapy with or without radiotherapy did not improve disease-free survival in newly diagnosed high-risk endometrial cancer.

Researchers missed hitting their goal regarding a Keytruda regimen in certain patients with endometrial cancer.

The phase 3 KEYNOTE-B21 clinical trial, evaluating Keytruda (pembrolizumab) plus chemotherapy with or without radiotherapy, did not meet its goal of improving disease-free survival (DFS) in patients with newly diagnosed, high-risk endometrial cancer who underwent surgery for curative intent, according to a press release from Merck, the manufacturer of Keytruda.

DFS, according to the National Cancer Institute, is the time after treatment when patients live without signs or symptoms of their cancer.

KEYNOTE-B21 compared post-surgical Keytruda plus chemotherapy with or without radiotherapy to a placebo (inactive drug) plus chemotherapy with or without radiotherapy in approximately 1,095 patients with high-risk endometrial cancer. All patients in the study had to have undergone a hysterectomy (surgical removal of the uterus) and bilateral salpingo-oophorectomy (surgical removal of both ovaries and fallopian tubes).

The study had two main goals: DFS and overall survival (OS), which is the time patients live before death of any cause. However, according to the press release, since DFS was not superior in the Keytruda-containing group, the researchers did not formally test OS.

“While these results were not what we had hoped, we are focused on continuing to build on the established role of Keytruda in advanced endometrial carcinoma through our approved indications, while rapidly progressing clinical research evaluating Keytruda-based combinations and other investigational candidates, including antibody-drug conjugates, in endometrial and other types of gynecologic malignancies,” Dr. Gursel Aktan, vice president, global clinical development, Merck Research Laboratories, said in the press release.

Keytruda is currently approved in combination with chemoradiotherapy for patients with stage 3-4A cervical cancer. It is also approved as a single agent for patients with PD-L1—positive recurrent or metastatic cervical cancer that progressed on or after chemotherapy. Of note, PD-L1 is a protein found on some cancer cells. Keytruda works by inhibiting that protein, which thereby allows the immune system to find and attack the cancer cells.

In the endometrial cancer space, the immunotherapy drug is approved for patients whose tumors are microsatellite instability-high (MSI-H) or DNA mismatch repair deficient (dMMR), which occurs when the protein responsible for repairing errors in cells does not function properly.

For patients without MSI-H or dMMR endometrial cancer, Keytruda is approved in combination with Lenvima (lenvatinib).

In KEYNOTE-B21, the safety profile of Keytruda was consistent with what was observed in prior studies of the drug, with no new side effects observed. According to the press release, researchers are still working on a full evaluation of the data.

More studies of the agent are still ongoing, such as the KEYNOTE-868 trial, which is analyzing Keytruda in combination with standard-of-care chemotherapy, followed by Keytruda alone for the treatment of primary advanced or recurrent endometrial cancer. Findings from this study are being reviewed by the Food and Drug Administration for potential approval.

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