The combination of pembrolizumab (Keytruda, Merck) and chemoradiotherapy has demonstrated a significant improvement in overall survival (OS) for women with high-risk locally advanced cervical cancer, according to results from a randomized phase 3 trial presented at the European Society for Medical Oncology (ESMO) Congress 2024. These findings reinforce the regimen as a potential new standard of care for this patient population.
The study, led by Domenica Lorusso, MD, PhD, director of the gynecologic oncology unit at Humanitas San Pio X in Italy, enrolled 1,060 women with stage IB2 to IIB (lymph node-positive) or stage III to IVA cervical cancer who had not previously received definitive surgery, radiation, or systemic therapy. Participants were randomized to receive either pembrolizumab plus chemoradiotherapy or placebo plus chemoradiotherapy.
Key Findings on Overall Survival
After a median follow-up of 29.9 months (range, 12.8-43), the pembrolizumab arm showed a significantly higher 36-month OS rate compared to the placebo arm (82.6% vs. 74.8%; HR = 0.67; 95% CI, 0.5-0.9). The median OS was not reached in either group at the time of analysis. This survival benefit was generally consistent across prespecified subgroups, including those with stage IB2 to IIB disease (HR = 0.89; 95% CI, 0.55-1.44) and stage III to IVA disease (HR = 0.57; 95% CI, 0.39-0.83).
Background and Study Design
The FDA had previously granted approval to pembrolizumab in combination with chemoradiotherapy in January based on progression-free survival (PFS) data from the double-blind NGOT-cx11/ GOG-3047/KEYNOTE-A18 study. In this trial, 529 women received 200 mg IV pembrolizumab every 3 weeks for five cycles concurrent with 40 mg/m2 IV cisplatin for five cycles with radiotherapy, followed by 400 mg IV pembrolizumab every 6 weeks for 15 cycles, while 531 women received placebo instead of pembrolizumab. Progression-free survival (PFS) and overall survival (OS) served as dual primary endpoints.
Safety Profile
The safety profile of the pembrolizumab regimen was deemed manageable, although a higher percentage of women in the pembrolizumab arm experienced grade 3 or higher treatment-related adverse events compared to the placebo arm (69.1% vs. 61.3%).
Clinical Implications
These overall survival results, coupled with the previously reported PFS benefits, support the integration of pembrolizumab into the standard treatment approach for women with high-risk locally advanced cervical cancer. Domenica Lorusso and colleagues suggest that pembrolizumab plus chemoradiotherapy should be considered the new standard of care for this population.
