Trial results for the KEYNOTE-A18 study (NCT04221945) investigating pembrolizumab in combination with chemoradiotherapy for locally advanced cervical cancer were posted on ClinicalTrials.gov on 2026-01-05. The study demonstrated that the combination significantly improved progression-free survival with a hazard ratio of 0.72 (p=0.0004) and overall survival with a hazard ratio of 0.73 (p=0.0076) compared to chemoradiotherapy alone.
Background
The KEYNOTE-A18 study, also known as "Study of Chemoradiotherapy With or Without Pembrolizumab (MK-3475) For The Treatment of Locally Advanced Cervical Cancer (MK-3475-A18/KEYNOTE-A18/ENGOT-cx11/GOG-3047)," aimed to evaluate the efficacy and safety of pembrolizumab plus concurrent chemoradiotherapy compared to placebo plus concurrent chemoradiotherapy in participants with locally advanced cervical cancer.
Trial design
The KEYNOTE-A18 study (NCT04221945) was a Phase 3, randomized trial that enrolled 1060 participants. The study investigated pembrolizumab plus concurrent chemoradiotherapy compared to placebo plus concurrent chemoradiotherapy in participants with locally advanced cervical cancer (Uterine Cervical Neoplasms). Participants received either pembrolizumab plus concurrent chemoradiotherapy (including cisplatin) or placebo for pembrolizumab plus concurrent chemoradiotherapy (including cisplatin). The primary hypotheses were that pembrolizumab plus concurrent chemoradiotherapy would be superior to placebo plus concurrent chemoradiotherapy with respect to progression-free survival and overall survival.
Key results
The trial results demonstrated improvements in progression-free survival (PFS) and overall survival (OS) with pembrolizumab plus chemoradiotherapy compared to placebo plus chemoradiotherapy.
- For Progression-Free Survival (PFS) as assessed by the investigator, the median PFS was 47.6 Months for the Chemoradiotherapy + Pembrolizumab group and 47.5 Months for the Chemoradiotherapy + Placebo for Pembrolizumab group. At Month 24, 70.6 Percentage of Participants in the Chemoradiotherapy + Pembrolizumab group achieved PFS, compared to 59.7 Percentage of Participants in the Chemoradiotherapy + Placebo for Pembrolizumab group. The hazard ratio (HR) for PFS was 0.72 (95% Confidence Interval: 0.59 to 0.87), with a p-value of 0.0004.
- For Progression-Free Survival (PFS) as assessed by Blinded Independent Central Review (BICR), the median PFS was 48.9 Months for the Chemoradiotherapy + Pembrolizumab group. At Month 24, 76.0 Percentage of Participants in the Chemoradiotherapy + Pembrolizumab group achieved PFS, compared to 68.1 Percentage of Participants in the Chemoradiotherapy + Placebo for Pembrolizumab group. The hazard ratio (HR) for PFS was 0.72 (95% Confidence Interval: 0.58 to 0.89), with a p-value of 0.0011.
- For Overall Survival (OS) at Month 36, 81.8 Percentage of Participants in the Chemoradiotherapy + Pembrolizumab group were alive, compared to 74.4 Percentage of Participants in the Chemoradiotherapy + Placebo for Pembrolizumab group. The hazard ratio (HR) for OS was 0.73 (95% Confidence Interval: 0.57 to 0.94), with a p-value of 0.0076.
Additional analyses showed a difference in survival rate at Month 36 of 7.4 (95% Confidence Interval: 2.3 to 12.5) for OS.
What this means
The results from the KEYNOTE-A18 trial indicate that adding pembrolizumab to concurrent chemoradiotherapy significantly improves both progression-free survival and overall survival in patients with locally advanced cervical cancer. The statistically significant hazard ratios and the higher percentages of participants achieving PFS at 24 months and OS at 36 months in the pembrolizumab arm suggest a meaningful clinical benefit. These findings provide important data for clinicians considering treatment strategies for locally advanced cervical cancer, potentially supporting the use of pembrolizumab in this setting.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT04221945, titled "Study of Chemoradiotherapy With or Without Pembrolizumab (MK-3475) For The Treatment of Locally Advanced Cervical Cancer (MK-3475-A18/KEYNOTE-A18/ENGOT-cx11/GOG-3047)," were posted on 2026-01-05 on clinicaltrials.gov.