KEYTRUDA® Plus LENVIMA® Shows Durable 5-Year Survival Benefit vs. Chemotherapy in Advanced Endometrial Carcinoma After Prior Platinum Therapy

“`html

10/18/2025 – 06:00 AM

At five years, KEYTRUDA plus LENVIMA showed a 16.7% overall survival (OS) rate for these patients with mismatch repair proficient (pMMR) advanced endometrial carcinoma versus 7.3% for chemotherapy alone in the pivotal Phase 3 KEYNOTE-775/Study 309 trial

Five-year OS results in the pMMR subgroup were consistent with the all-comers study population, which demonstrated an OS rate of 19.9% for KEYTRUDA plus LENVIMA versus 7.7% for chemotherapy

RAHWAY, N.J. & NUTLEY, N.J.–Merck (NYSE: MRK) and Eisai today announced long-term follow-up data showing a sustained benefit of KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, in combination with LENVIMA (lenvatinib), Eisai’s oral multiple receptor tyrosine kinase inhibitor (TKI), compared to chemotherapy for patients with advanced endometrial carcinoma. These patients had previously undergone at least one platinum-based regimen. The findings, stemming from five years of follow-up in the Phase 3 KEYNOTE-775/Study 309 trial, compared KEYTRUDA plus LENVIMA versus chemotherapy (physician’s choice of doxorubicin or paclitaxel) in advanced endometrial carcinoma patients, and were presented at the European Society for Medical Oncology (ESMO) Congress 2025 in Berlin, Germany (Presentation #1119P).

The study randomized 827 patients, comprising 697 with mismatch repair proficient (pMMR) cancer and 130 with mismatch repair deficient (dMMR) cancer, to receive KEYTRUDA plus LENVIMA (n=411) or chemotherapy (n=416). The trial’s primary endpoints, overall survival (OS) and progression-free survival (PFS), were evaluated in patients with pMMR disease and in the intent-to-treat (ITT) population, which included all randomized patients.

For the pMMR subgroup, the five-year OS rate was 16.7% for KEYTRUDA plus LENVIMA versus 7.3% for chemotherapy alone, after a median follow-up of 68.8 months (range, 60.8–79.0 months for KEYTRUDA plus LENVIMA; range, 60.9–80.0 for chemotherapy). Median OS was 18.0 months (95% CI, 14.9-20.5) for the combination therapy versus 12.2 months (95% CI, 11.0-14.1) for chemotherapy alone (HR 0.70; 95% CI, 0.60-0.83). Five-year OS results in the pMMR subgroup were consistent with the all-comers population, which demonstrated an OS rate of 19.9% for KEYTRUDA plus LENVIMA versus 7.7% for chemotherapy; median OS was 18.7 months (95% CI, 15.6-21.3) for KEYTRUDA plus LENVIMA versus 11.9 months (95% CI, 10.6-13.3) for chemotherapy (HR 0.66; 95% CI, 0.57-0.77).

These extended survival data offer a significant improvement over chemotherapy alone, potentially reshaping treatment paradigms for this aggressive cancer. However, the combination therapy also presents challenges in terms of adverse events, requiring careful patient selection and management.

The observed long-term OS data aligned with initial findings presented at the Society of Gynecologic Oncology (SGO) 2021 Annual Meeting and published in the _New England Journal of Medicine_. The primary analysis reported a median OS of 17.4 months (95% CI, 14.2-19.9) for KEYTRUDA plus LENVIMA versus 12.0 months (95% CI, 10.8-13.3) for chemotherapy within the pMMR subgroup, and 18.3 months (95% CI, 15.2-20.5) versus 11.4 months (95% CI, 10.5-12.9) in the all-comers population. The latest five-year analysis revealed no new safety concerns, with the safety profile of KEYTRUDA plus LENVIMA mirroring previously reported data.

Dr. Vicky Makker, Principal Investigator and Gynecologic Medical Oncologist, Memorial Sloan Kettering Cancer Center, emphasized the importance of these findings: “Endometrial carcinoma is difficult-to-treat in the recurrent or advanced stage, especially when tumors are mismatch repair proficient and therefore harder to target with immunotherapy alone. Five-year follow-up data from the KEYNOTE-775/Study 309 trial show sustained survival benefit in patients treated with pembrolizumab plus lenvatinib and underscore the role of this combination as an effective treatment option for patients with advanced endometrial carcinoma who need further treatment after receiving prior platinum-based therapy.”

Dr. Gregory Lubiniecki, Vice President, Global Clinical Development, Merck Research Laboratories, noted Merck’s dedication to addressing women’s cancers: “Recent advances have led to steady improvement in outcomes for patients with advanced endometrial carcinoma. These five-year data highlight the durable survival benefit of KEYTRUDA plus LENVIMA in patients with advanced endometrial carcinoma who have received prior platinum-based therapy and are the result of our ongoing commitment to delivering impactful treatment options for people affected by women’s cancers.”

“The five-year results from KEYNOTE-775/Study 309 represent the longest reported follow-up for a trial evaluating an immunotherapy plus tyrosine kinase inhibitor combination in advanced endometrial carcinoma,” said Dr. Corina Dutcus, Senior Vice President, Oncology Global Clinical Development Lead at Eisai Inc., highlighting the combination’s therapeutic value.

Analysts note that while these results are promising, the combination therapy carries a substantial side effect burden. Treatment-related adverse events (TRAEs) occurred in 97.3% of patients receiving KEYTRUDA plus LENVIMA versus 93.8% of patients receiving chemotherapy, leading to the discontinuation of KEYTRUDA and/or LENVIMA in 40.1% of patients (16.0% discontinued both drugs) compared to 8.0% of chemotherapy patients. Common adverse events (≥ 20%) in the KEYTRUDA plus LENVIMA group included hypertension (61.8%), hypothyroidism (55.7%), diarrhea (43.3%), nausea (40.1%), decreased appetite (37.9%), fatigue (28.8%), proteinuria (27.6%), vomiting (24.4%), arthralgia (23.9%), decreased weight (22.7%), and palmar-plantar erythrodysesthesia syndrome (20.7%).

Based on the 2021 primary analysis results, KEYTRUDA plus LENVIMA is approved in the U.S. for patients with advanced endometrial carcinoma that is pMMR or not microsatellite instability-high (MSI-H), who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation. It is also approved in the European Union (EU) and Japan for specific patients with advanced or recurrent endometrial carcinoma, regardless of mismatch repair status.

The KEYNOTE-775/Study 309 trial’s detailed data are crucial for physicians in tailoring treatment strategies for advanced endometrial carcinoma, balancing efficacy with potential adverse effects. The results underscore the potential of combination therapies in addressing cancers with limited treatment options, while emphasizing the need for precision in patient selection and comprehensive management of treatment-related toxicities.

KEYTRUDA is projected to remain a significant revenue driver for Merck, while LENVIMA contributes to Eisai’s oncology portfolio. The ongoing LEAP clinical program, evaluating KEYTRUDA plus LENVIMA across various cancer types, could further expand their combined market presence, but faces competitive pressures from other emerging immunotherapies and targeted agents. Investors will be closely watching future clinical trials and real-world usage data to assess the long-term impact of this combination therapy on patient outcomes and market dynamics.

• KEYTRUDA (200 mg intravenously every three weeks) plus LENVIMA (20 mg orally once daily); or

• Investigator’s choice, consisting of either doxorubicin (60 mg/m² every three weeks) or paclitaxel (80 mg/m² given weekly, three weeks on/one week off).

“`