KEYNOTE-A18: pembrolizumab with chemoradiotherapy for locally advanced cervical cancer (overall survival)
The second report from KEYNOTE-A18 showed that adding pembrolizumab to chemoradiotherapy for high-risk locally advanced cervical cancer also lengthened life: 82.6% of women were alive at three years against 74.8%, a third fewer deaths.
Overview
Second interim analysis of the double-blind, placebo-controlled phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 trial, in which 1,060 patients with newly diagnosed, high-risk locally advanced cervical cancer (FIGO 2014 stage IB2-IIB node-positive or stage III-IVA) were randomised to pembrolizumab or placebo with cisplatin-based chemoradiotherapy followed by pembrolizumab or placebo maintenance.
At data cutoff on 8 January 2024 (median follow-up 29.9 months) median overall survival was not reached in either group; 36-month overall survival was 82.6% with pembrolizumab against 74.8% with placebo, hazard ratio for death 0.67 (p=0.0040), meeting the primary objective. Grade 3 or higher adverse events occurred in 78% and 70% of patients, and potentially immune-mediated adverse events in 39% and 17%. Together with the progression-free survival report it established immuno-chemoradiotherapy as a new standard of care for this population.
- 36-month overall survival 82.6% (95% CI 78.4-86.1) vs 74.8% (70.1-78.8); HR for death 0.67 (95% CI 0.50-0.90, p=0.0040).
- Median follow-up 29.9 months; median overall survival not reached in either group.
- Grade 3 or higher adverse events 78% vs 70%, most often anaemia and falls in white cell and neutrophil counts.
- Potentially immune-mediated adverse events 39% vs 17%.
The survival gain turns the earlier progression-free survival result into a clear reason to offer pembrolizumab with and after chemoradiotherapy to women with node-positive or stage III-IVA cervical cancer. Because cervical cancer is concentrated in low- and middle-income countries, the benefit reaches most women only if pricing and access follow.
- Interim analysis with median follow-up under three years; late recurrences are possible in this disease.
- High-risk population only; the negative CALLA trial suggests lower-risk patients may not benefit.
- About two years of pembrolizumab is costly where cervical cancer burden is highest.
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