Update on safety and feasibility of the combination of pembrolizumab and pelvic chemoradiation in locally advanced cervical cancer
Mené sur 94 patientes atteintes d'un cancer du col de l'utérus localement avancé, cet essai de phase II évalue la sécurité, du point de vue de l'incidence et de la gravité des événements indésirables, et la faisabilité d'un ajout de pembrolizumab à une radiothérapie pelvienne, concomitante ou séquentielle
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.