As reported in The Lancet by Lorusso et al, overall survival results from the phase III ENGOT-cx11/GOG-3047/KEYNOTE-A18 trial indicated a significant benefit of pembrolizumab vs placebo with concurrent chemoradiotherapy followed by pembrolizumab vs placebo in patients with newly diagnosed, high-risk, locally advanced cervical cancer.
At the first interim analysis of the trial, the addition of pembrolizumab to chemoradiotherapy was associated with a significant improvement in progression-free survival.
Study Details
In the double-blind trial, 1,060 patients from sites in 30 countries were randomly assigned between June 2020 and December 2022, to receive 5 cycles of pembrolizumab at 200 mg (n = 529) or placebo (n = 531) every 3 weeks with concurrent chemoradiotherapy, followed by 15 cycles of pembrolizumab at 400 mg or placebo every 6 weeks. Chemoradiotherapy consisted of five cycles of cisplatin at 40 mg/m2 once weekly plus external-beam radiotherapy followed by brachytherapy. The primary endpoints were progression-free survival and overall survival.
Key Findings
At the protocol-specified second interim analysis (data cutoff in January 2024), median follow-up was 29.9 months (interquartile range = 23.3–34.3 months). At the second interim analysis, median overall survival was not reached in either group. Overall survival rate at 36 months was 82.6% (95% confidence interval [CI] = 78.4%–86.1%) in the pembrolizumab group vs 74.8% (95% CI = 70.1%–78.8%) in the control group (hazard ratio [HR] = 0.67, 95% CI = 0.50–0.90, P = .0040). Disease-specific survival at 3 years was 86.8% (95% CI = 83.1%–89.7%) in the pembrolizumab group vs 79.0% (95% CI = 74.6%–82.8%) in the control group (HR = 0.64, 95% CI = 0.46–0.89).
The investigators concluded: “Pembrolizumab plus chemoradiotherapy significantly improved overall survival in patients with locally advanced cervical cancer. These data, together with results from the first interim analysis, support this immunochemoradiotherapy strategy as a new standard of care for this population.”
Domenica Lorusso, MD, PhD, of the Gynaecology Oncology Unit, Humanitas San Pio X, Milan, is the corresponding author of The Lancet article.
Disclosure: The study was funded by Merck Sharp & Dohme, a subsidiary of Merck & Co. For full disclosures of the study authors, visit thelancet.com.
