The European Commission has granted approval to pembrolizumab (Keytruda)-based regimens for two gynecologic cancer indications, specifically for patients within the European Union. This decision, announced by Merck, follows positive recommendations from the European Medicine Agency’s Committee for Medicinal Products for Human Use in September 2024.
The approved regimens include pembrolizumab in combination with carboplatin and paclitaxel as a first-line treatment for adults with primary advanced or recurrent endometrial carcinoma who are eligible for systemic therapy. Additionally, pembrolizumab plus chemoradiotherapy (CRT) has been approved for adults with previously untreated International Federation of Gynecology and Obstetrics (FIGO) 2014 stage III to IVA locally advanced cervical cancer.
Dr. Gursel Aktan, VP of Global Clinical Development at Merck Research Laboratories, stated that these pembrolizumab-based regimens could potentially transform the treatment landscape for patients with endometrial and cervical cancer, two of the most frequently diagnosed cancers among women in Europe. He emphasized that these approvals highlight the expanding utility of pembrolizumab across diverse patient populations and treatment settings, from earlier lines of therapy to advanced disease management.
Supporting Clinical Trials
The approval for the endometrial carcinoma indication was based on the phase 3 NRG-GY018/KEYNOTE-868 trial (NCT03914612). The cervical cancer approval was supported by data from the phase 3 KEYNOTE-A18 trial (NCT04221945).
KEYNOTE-868 Trial
Results from the KEYNOTE-868 trial demonstrated that pembrolizumab combined with chemotherapy significantly improved progression-free survival (PFS) compared to chemotherapy alone in patients with mismatch repair proficient (pMMR) endometrial carcinoma. In a cohort of 591 patients with pMMR endometrial carcinoma, the median PFS was 13.1 months (95% CI, 10.5-18.8) with pembrolizumab/chemotherapy versus 8.7 months (95% CI, 8.4-10.7) with chemotherapy alone (HR, 0.54; 95% CI, 0.41-0.71; P < .00001). Among 225 evaluable patients with mismatch repair deficient (dMMR) disease, the median PFS was not reached (NR; 95% CI, 30.6-NR) and 7.6 months (95% CI, 6.4-9.9) in each respective treatment arm (HR, 0.30; 95% CI, 0.19-0.48; P < .00001).
The KEYNOTE-868 trial involved patients with stage III, IVA, IVB, or recurrent endometrial cancer who were randomly assigned to receive either pembrolizumab (200 mg intravenously every 3 weeks) or placebo plus paclitaxel (175 mg/m2) and carboplatin (AUC 5) for 6 cycles, followed by pembrolizumab (400 mg intravenously) or placebo every 6 weeks for a maximum of 14 cycles. The primary endpoint was PFS, with secondary endpoints including overall survival (OS), objective response rate (ORR), duration of response, and safety.
KEYNOTE-A18 Trial
In the KEYNOTE-A18 trial, combining pembrolizumab with CRT in patients with stage III to IVA cervical cancer reduced the risk of disease progression or death by 41% compared to CRT alone (HR, 0.59; 95% CI, 0.43-0.82). Prior data also indicated that the pembrolizumab combination reduced the risk of death by 33% (HR, 0.67; 95% CI, 0.50-0.90; P = .0040).
The KEYNOTE-A18 trial included 1060 patients with previously untreated cervical cancer who were assigned to receive either pembrolizumab (200 mg intravenously every 3 weeks) or placebo for 5 cycles plus cisplatin (40 mg/m2 every week for 5 cycles) and radiotherapy, followed by pembrolizumab (400 mg intravenously) or placebo every 6 weeks for 15 cycles. The primary endpoints were PFS and OS, with secondary endpoints including complete response rate, ORR, and safety.
