Keytruda with chemo fails as post-surgery therapy for new endometrial cancer

Merck & Co.'s Keytruda, a PD-1 inhibitor, has faced a setback in its role as an adjuvant treatment for newly diagnosed high-risk endometrial cancer. The KEYNOTE-B21 study's interim analysis revealed that combining Keytruda with chemotherapy—whether or not accompanied by radiotherapy—failed to achieve the desired results for disease-free survival (DFS). DFS measures the duration a patient remains free of cancer symptoms post-primary treatment. Due to this shortfall, the trial's other primary endpoint, overall survival, wasn't formally tested.

Despite this outcome, Merck is conducting a full evaluation of the trial data and plans to release the results at a future date. Endometrial cancer ranks as the sixth most prevalent cancer in women globally and is the leading cancer type in the uterus. Merck predicts approximately 67,880 new cases of uterine body cancer in the U.S. alone this year, with an estimated 13,250 related deaths in 2024.

Gursel Aktan, M.D., Ph.D., vice president of global clinical development at Merck Research Laboratories, expressed disappointment but remained focused on expanding Keytruda's established role in treating advanced endometrial carcinoma. Aktan emphasized Merck's commitment to continue exploring Keytruda-based combinations and other treatment modalities like antibody-drug conjugates (ADC) for endometrial and other gynecologic cancers.

Keytruda is already approved for endometrial carcinoma patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors. This approval came in 2022, following an earlier 2017 nod for treating previously managed MSI-H/dMMR tumors in patients lacking alternative treatment options. Additionally, Keytruda is also approved in conjunction with Lenvima, a drug developed in collaboration with Eisai, for previously treated endometrial cancer that isn’t dMMR.

The competition in the endometrial cancer treatment space has been intense, notably between Keytruda and GSK’s PD-1 rival Jemperli. Last year, Jemperli achieved a significant milestone by gaining approval for immunotherapy in first-line endometrial cancer. Subsequently, in February, Keytruda combined with standard chemotherapy demonstrated its efficacy in slowing tumor progression or death in advanced or recurrent endometrial cancer, outperforming chemotherapy alone. In March, at the Society of Gynecologic Oncology 2023 annual meeting, Merck and GSK showcased the performance of their respective drugs in first-line endometrial cancer. Keytruda seemed to have an edge over Jemperli in MMR proficient (pMMR) patients, a key subgroup that constitutes about two-thirds of all endometrial cancer cases.

However, in July, GSK's Jemperli secured FDA clearance as an adjunct to chemotherapy for newly diagnosed advanced or recurrent endometrial cancer, specifically for tumors that are dMMR or MSI-H. In contrast, Merck and Eisai’s Keytruda-Lenvima combination missed its primary endpoints in a phase 3 study conducted as a first-line treatment for specific cases of advanced or recurrent endometrial carcinoma. The regimen failed to show an improvement in overall survival and progression-free survival compared to platinum-based chemotherapy.

Keytruda, although reaching the top of pharma’s sales charts in 2023, has experienced mixed clinical outcomes in 2024. The year began with a partial success in a phase 3 trial for high-risk localized muscle-invasive bladder cancer. Around the same time, Keytruda demonstrated promising results as a postsurgical treatment for resectable kidney cancer, reducing the risk of death by 38% versus placebo in patients with clear cell renal carcinoma. Keytruda also posted positive results in cervical cancer in March. However, its combination with Lynparza failed to outperform chemotherapy in prolonging life expectancy or delaying disease progression in newly diagnosed metastatic nonsquamous non-small cell lung cancer.