Pembrolizumab Plus Lenvatinib Show Promise in Advanced Endometrial Carcinoma

New results from the pivotal phase 3 KEYNOTE-775/Study 309 found statistically significant improvements in overall survival (OS) and progression-free survival (PFS) with the combination of pembrolizumab (Keytruda; Merck) and lenvatinib (Lenvima; Eisai) in patients with advanced endometrial carcinoma following at least 1 prior platinum-based regimen in any setting.

Researchers investigated the combination of pembrolizumab plus lenvatinib versus chemotherapy. The trial had dual primary endpoints of OS and PFS, and additional data on objective response rate (ORR), efficacy, and safety were recently published in the New England Journal of Medicine.

“While rates of endometrial carcinoma continue to rise globally, patients with advanced or recurrent disease have limited options available to them once the disease progresses following platinum-based chemotherapy,” said Gregory Lubiniecki, MD, vice president of oncology clinical research at Merck Research Laboratories, in a press release.

Endometrial carcinoma begins in the inner lining of the uterus and is the most common type of uterine cancer. In 2020, there were an estimated 417,000 new cases of endometrial carcinoma diagnosed worldwide and more than 97,000 deaths, according to the press release. The 5-year relative survival rate for metastatic endometrial carcinoma is estimated to be approximately 17%.

KEYNOTE-775/Study 309 is a phase 3, multicenter, open-label, randomized, active-controlled trial conducted in 827 patients. Participants may have received up to 2 platinum-containing therapies in total, if 1 of the treatments was administered in the neoadjuvant or adjuvant setting. Patients were excluded if they had endometrial sarcoma, carcinosarcoma, pre-existing grade 3 or higher fistula, uncontrolled blood pressure, significant cardiovascular impairment or even within the previous 12 months, or if they had active autoimmune disease or a condition requiring immunosuppression.

Patients were randomized 1:1 to receive pembrolizumab 200 mg intravenously every 3 weeks plus lenvatinib 20 mg orally once daily or investigator’s choice of doxorubicin or paclitaxel. Treatment with pembrolizumab and lenvatinib continued until progression of disease, unacceptable toxicity, or for a maximum of 24 months with pembrolizumab.

“KEYNOTE-775/Study 309 is an important phase 3 study that supported recent approvals of Keytruda plus Lenvima for certain types of advanced endometrial carcinoma in the US and other countries around the world, where it became the first immunotherapy and tyrosine kinase inhibitor combination approved for these patients,” Lubiniecki said in the press release.

Based on the results from the phase 3 KEYNOTE-775/Study 309 trial, the FDA approved pembrolizumab plus lenvatinib for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability-high or deficient mismatch repair, who have disease progression following prior systemic therapy in any setting, and who are not candidates for curative surgery or radiation. Researchers are continuing to investigate the combination in more than 10 different tumor types across more than 20 clinical trials, according to the press release.

REFERENCE

Results from pivotal phase 3 KEYNOTE-775/Study 309 trial of Keytruda (pembrolizumab) plus Lenvima (lenvatinib) in advanced endometrial carcinoma published in the New England Journal of Medicine. News release. Merck; January 20, 2022. Accessed January 20, 2022. https://www.merck.com/news/results-from-pivotal-phase-3-keynote-775-study-309-trial-of-keytruda-pembrolizumab-plus-lenvima-lenvatinib-in-advanced-endometrial-carcinoma-published-in-the-new-england-journal-of-med/