Dr Duska on the Role of Immunotherapy With Definitive Treatment in High-Risk, Locally Advanced Cervical Cancer

"The study had two preplanned interim analyses. [The first was conducted] very early in the study, when the median follow-up was approximately 18 months. [At that time], the study met its PFS end point…The experimental arm had improved PFS over the placebo arm, even that early in the study, with a hazard ratio of around [0.7]. [That was very promising], and we were really excited about that."

Linda R. Duska, MD, MPH, professor of gynecologic oncology at the University of Virginia, highlighted the significance of incorporating immunotherapy into definitive treatment for patients with high-risk, locally advanced cervical cancer following the read out of final results from the phase 3 KEYNOTE-A18 trial (NCT04221945), which evaluated pembrolizumab (Keytruda) in combination with concurrent chemoradiotherapy (CRT) vs placebo plus CRT in this patient population.

Findings from the final analysis, which was descriptive in nature, that were presented at the 2025 ASCO Annual Meeting showed that at a median follow-up of 41.9 months, the pembrolizumab-based regimen reduced the risk of disease progression or death by 28% compared with the placebo regimen (HR, 0.72; 95% CI, 0.59-0.87). A similar benefit was observed regarding overall survival (OS; HR, 0.73; 95% CI, 0.57-0.94)

Duska noted that during the first preplanned interim analysis, conducted at a median follow-up of 18.2 months, the trial met its primary progression-free survival (PFS) end point (HR, 0.70; 95% CI, 0.55-0.89, P = .0020). Based on the study’s hierarchical statistical design, all alpha was initially allocated to PFS; following significance in this end point, testing proceeded to OS.

At the second interim analysis, conducted at a median follow-up of 29.9 months, the trial met the OS end point (HR, 0.67; 95% CI, 0.50-0.90; P = .0040), Duska emphasized that despite early censoring in both interim analyses, the data demonstrated consistent benefit across efficacy outcomes.

In January 2024, the FDA approved pembrolizumab plus chemoradiation for patients with FIGO 2014 stage III to IVA cervical cancer, based on prior data from KEYNOTE-A18.