Pembrolizumab Plus Chemotherapy for Cervical Cancer: An Exploratory Analysis of the KEYNOTE-826 Randomized Clinical Trial.

Abstract

Importance In the KEYNOTE-826 study, pembrolizumab (vs placebo) plus platinum-based chemotherapy (with or without bevacizumab) significantly improved progression-free survival and overall survival in participants with previously untreated persistent, recurrent, or metastatic cervical cancer at interim analysis 1 (median follow-up, 22.0 months), with continued benefit at final analysis (median follow-up, 39.1 months). Long-term follow-up is important to further inform the benefit-risk profile of anticancer treatments. Objective To investigate 5-year efficacy and safety results of pembrolizumab plus chemotherapy (with or without bevacizumab) in previously untreated persistent, recurrent, or metastatic cervical cancer. Design, Setting, and Participants This ad hoc exploratory analysis of the phase 3, double-blind KEYNOTE-826 randomized clinical trial was conducted in participants with previously untreated persistent, recurrent, or metastatic cervical cancer across 151 sites in 19 countries. Participants were randomly assigned to treatment between November 20, 2018, and January 31, 2020. The median follow-up for this analysis was 59.1 (range, 52.1-66.5) months (approximately 20 months after final analysis). Data were analyzed between November 20, 2018, and June 4, 2024. Interventions Pembrolizumab, 200 mg, every 3 weeks for up to 35 cycles vs placebo, each combined with platinum-based chemotherapy (with or without bevacizumab). Main Outcomes and Measures Progression-free survival and overall survival. Results A total of 617 female patients were randomized. At baseline, the median age of participants was 51.0 (range, 22-82) years, with 303 participants (49.1%) having stage I/II and 190 (30.8%) having IVB disease and 446 (72.3%) having squamous cell/squamous cell carcinoma. At 5 years, the overall survival benefit was sustained with pembrolizumab plus chemotherapy in the programmed cell death ligand 1 combined positive score of at least 1 (median [IQR], 28.6 [12.3 to not reached] vs 16.5 [9.0-40.5] months; hazard ratio [HR], 0.62 [95% CI, 0.50-0.76]) and intention-to-treat (median [IQR], 26.4 [12.0 to not reached] vs 16.8 [9.1-40.1] months; HR, 0.64 [95% CI, 0.53-0.78]) populations. The progression-free survival advantage was similarly maintained (median [IQR], 10.5 [6.2 to not reached] vs 8.2 [4.2-17.1] months; HR, 0.58 [95% CI, 0.48-0.71] and median [IQR], 10.4 [6.2 to not reached] vs 8.2 [4.3-15.5] months; HR, 0.61 [95% CI, 0.51-0.74], respectively). No new safety signals were observed. No additional deaths due to treatment-related adverse events had occurred since the final analysis. Conclusions and Relevance In this exploratory analysis of the KEYNOTE-826 randomized clinical trial, the 5-year data confirm the durability of benefit and reinforce pembrolizumab plus chemotherapy (with or without bevacizumab) as a first-line standard-of-care option for recurrent and metastatic cervical cancer. Trial Registration ClinicalTrials.gov Identifier: NCT03635567.