Five-year follow-up from the phase III KEYNOTE-826 trial suggests a durable benefit with first-line pembrolizumab plus platinum-based chemotherapy, with or without bevacizumab, in patients with recurrent or metastatic cervical cancer, according to Hasegawa et al in JAMA Oncology.
At the first interim analysis, conducted after a median follow-up of 22.0 months, significant improvements in both progression-free and overall survival were observed vs placebo. These benefits were maintained through the final analysis after a median follow-up of 39.1 months, the investigators wrote.
“Long-term follow-up is important to further inform the benefit-risk profile of anticancer treatments,” they commented. Findings from the present ad hoc exploratory analysis “reinforce this treatment as a long-term standard-of-care option for patients with advanced cervical cancer.”
Study Details
In KEYNOTE-826, a total of 617 female patients (median age = 51.0 years) with previously untreated persistent, recurrent, or metastatic cervical cancer from 151 sites in 19 countries were randomly assigned to receive platinum-based chemotherapy, with or without bevacizumab, in combination with pembrolizumab (200 mg; every 3 weeks for ≤ 35 cycles) vs placebo.
The median duration of follow-up for this analysis was 59.1 months—approximately 20 months after the final analysis.
The investigators identified overall and investigator-assessed progression-free survival as dual primary endpoints.
Five-Year Results
At 5 years, the overall survival benefit with pembrolizumab plus chemotherapy vs placebo appeared to be sustained in both the PD-L1 combined positive score (CPS) of at least 1 population (median = 28.6 vs 16.5 months; hazard ratio [HR] = 0.62, 95% confidence interval [CI] = 0.50–0.76) and the intention-to-treat population (median = 26.4 vs 16.8 months; HR = 0.64, 95% CI = 0.53–0.78).
The progression-free survival benefit was similarly found to be maintained in both populations, with a median duration of 10.5 months with pembrolizumab plus chemotherapy vs 8.2 months with placebo in the PD-L1 CPS of at least 1 population (HR = 0.58, 95% CI = 0.48–0.71) and 10.4 vs 8.2 months, respectively, in the intention-to-treat population (HR = 0.61, 95% CI = 0.51–0.74).
The investigators reported no new safety signals. Since the final analysis, no additional deaths because of treatment-related adverse events were observed.
“In this exploratory analysis of the KEYNOTE-826 randomized clinical trial, 5-year results confirmed the durable benefit and consistent safety profile of pembrolizumab plus chemotherapy with or without bevacizumab…,” the investigators concluded.
Kosei Hasegawa, MD, PhD, of Saitama Medical University International Medical Center, Hidaka, Japan, is the corresponding author of the article in JAMA Oncology.
Disclosure: The work was funded by Merck Sharp & Dohme. For full disclosures of the study authors, visit jamanetwork.com.
