Phase 3 Trial Results of KEYTRUDA® (pembrolizumab) Plus LENVIMA® (lenvatinib) in Advanced Endometrial Carcinoma Published in The New England Journal of Medicine

Recently, MSD and Eisai announced positive results from a pivotal phase 3 clinical trial in the New England Journal of Medicine. The trial results met its dual primary endpoints, showing significant improvements in overall survival (OS) and progression-free survival (PFS) for patients with advanced endometrial cancer treated with the combination of anti-PD-1 therapy Keytruda and the oral multi-receptor tyrosine kinase inhibitor Lenvima compared to chemotherapy. Patients receiving the combination therapy had previously undergone treatment with at least one platinum-based chemotherapy regimen. In July last year, the U.S. FDA fully approved this combination therapy for the treatment of advanced endometrial cancer in patients who do not have microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR), whose disease progressed after prior systemic therapy, and who are not candidates for curative surgery or radiation.

Endometrial cancer is the most common type of cancer in the uterus. In 2020, there were an estimated over 417,000 new cases globally. The five-year survival rate for advanced metastatic endometrial cancer is approximately 17%, with limited treatment options currently available, representing a significant unmet clinical need.

Keytruda/Lenvima Combination Therapy is an important cancer immunotherapy jointly developed by MSD and Eisai. Keytruda is a humanized monoclonal antibody that blocks PD-1-mediated immunosuppressive signals, thereby activating T lymphocytes and enhancing the body's immune system’s ability to detect and combat tumor cells. Lenvima is a kinase inhibitor that suppresses the activity of vascular endothelial growth factor receptor VEGFR1/2/3. It can also inhibit other kinases involved in pathological angiogenesis, tumor growth, and cancer progression.

In this Phase 3 clinical trial, 827 patients were randomly assigned in a 1:1 ratio to receive either Keytruda + Lenvima or chemotherapy (doxorubicin or paclitaxel).

Trial data show that, compared to the chemotherapy group, the median PFS (7.2 months VS. 3.8 months) and median OS (18.3 months VS. 11.4 months) were significantly higher in the Keytruda/Lenvima group. In terms of safety, 88.9% of patients in the Keytruda/Lenvima group experienced grade 3 or higher adverse events, compared to 72.7% in the chemotherapy group.

References:

[1] 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. Retrieved January 20, 2022, from 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/

[2] Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer. Retrieved January 19, 2022, from https://www.nejm.org/doi/full/10.1056/NEJMoa2108330

(Original text has been abridged)

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