Pembrolizumab Improves Progression-Free Survival as First-Line Therapy for Advanced, Recurrent Endometrial Carcinoma

New results from the phase 3 NRG-GY018 show that pembrolizumab plus chemotherapy improved progression-free survival (PFS) as a first-line treatment for patients with stage 3 or 4 or recurrent endometrial carcinoma, regardless of mismatch repair status.

At a pre-specified interim analysis, pembrolizumab in combination with carboplatin and paclitaxel and then continued as a single agent every 6 weeks for up to 14 cycles demonstrated a statistically significant and clinically meaningful improvement in PFS compared with chemotherapy alone in patients whose endometrial carcinoma was either mismatch repair proficient (pMMR) or mismatch repair deficient (dMMR). The results will be presented at an upcoming medical meeting.

Endometrial carcinoma begins in the inner lining of the uterus and is the most common type of cancer in the uterus. It remains the only gynecologic malignancy with a rising incidence and mortality rate, with an estimated 66,000 new cases of uterine body cancer and approximately 13,000 deaths anticipated from the disease in the United States in 2023.

“Patients with advanced stage or recurrent endometrial cancer, the most common type of gynecologic cancer in the US, face a poor prognosis with limited treatment options,” said principal investigator Ramez Eskander, MD, in a press release. “This is particularly notable in patients who progress after prior platinum-based adjuvant therapy with disease not amenable to curative surgery or radiation.”

The randomized, blinded, placebo-controlled phase 3 trial evaluated pembrolizumab in combination with standard of care chemotherapy versus placebo plus standard of care chemotherapy alone. The primary endpoint is PFS, and secondary endpoints include overall survival, objective response rate, duration of response, and safety.

The trial enrolled 819 patients who were randomized to receive pembrolizumab plus chemotherapy every 3 weeks for approximately 6 cycles followed by pembrolizumab as a single agent every 6 weeks for up to 14 cycles, or placebo plus chemotherapy. Participants were required to have MMR testing prior to randomization and approximately 70% of patients were pMMR whereas approximately 30% were dMMR.

“In this study, pembrolizumab in combination with carboplatin and paclitaxel resulted in a statistically significant and clinically meaningful improvement in progression-free survival in both the dMMR and pMMR study populations,” Eskander said in the press release. “We look forward to presenting these exciting findings at an upcoming scientific congress.”

In the United States, pembrolizumab has 2 approved indications for endometrial cancer. First, it is approved in combination with lenvatinib for patients with advanced endometrial carcinoma that is pMMR or not microsatellite instability-high (MSI-H) who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.

Secondly, it is approved as a single agent for patients with advanced endometrial carcinoma that is MSI-H or dMMR who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.

“In certain patients with advanced endometrial cancer who have progressed following prior systemic therapy and are not candidates for surgery or radiation, Keytruda has become an important treatment option, both as monotherapy and in combination,” said Eliav Barr, MD, senior vice president, head of global clinical development, and chief medical officer at Merck Research Laboratories, in the press release. “These latest results in the first-line setting are very encouraging and show the potential of Keytruda plus chemotherapy for patients with stage 3 to 4 or recurrent disease regardless of mismatch repair status.”

REFERENCE

Merck’s Keytruda (pembrolizumab) plus chemotherapy met primary endpoint of progression-free survival (PFS) as first-line therapy for advanced or recurrent endometrial carcinoma. News release. Merck; February 3, 2023. Accessed February 9, 2023. https://www.merck.com/news/mercks-keytruda-pembrolizumab-plus-chemotherapy-met-primary-endpoint-of-progression-free-survival-pfs-as-first-line-therapy-for-advanced-or-recurrent-endometrial-carcinoma/