Background: The addition of immune checkpoint inhibitors to standard-of-care chemoradiation (CRT) is established as the new standard of care in high-risk, locally advanced cervical cancer. However, the optimal sequencing of therapies is unknown. Defining safety and feasibility of the combination was a primary objective of this study examining concurrent versus sequential schedules.
Methods: Pembrolizumab was given after or during CRT in a randomized phase 2 design. Patients aged 18 years and older with locally advanced cervical cancer, stages IB-IVA (according to 2009 International Federation of Gynecology and Obstetrics staging) were randomized 1:1 to treatment regimens. CRT was identical for both arms. Pembrolizumab was administered every 3 weeks for three doses; no maintenance was allowed. Safety assessments included the incidence and severity of adverse events (AEs), and feasibility was measured by the completion of treatment in a predefined timeframe. Translational specimens (blood and tissue) were collected.
Results: In total, 94 evaluable patients completed treatment. Treatment-related grade ≥2 toxicity was experienced by 85 of 94 patients (90%); 40 patients (43%) had at least one grade 3 AE, and 22 (23%) had at least one grade 4 AE. There were no grade 5 AEs. Eighty percent of patients completed radiotherapy within 56 days, and 85% completed five or six doses of cisplatin and three doses of pembrolizumab (74 of 94 patients; 79%).
Conclusions: The final results of this study support the safety and feasibility of adding pembrolizumab to pelvic CRT, concurrently and sequentially. Progression-free and overall survival were not affected or different between treatment arms. An analysis of the translational end points is ongoing and will inform future study designs.
Keywords: cervical cancer; chemoradiation; feasibility; immunotherapy; safety.
© 2025 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.