RESULTS of the phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study have been presented at ESMO 2024, Barcelona, Spain. The findings demonstrated that pembrolizumab combined with concurrent chemoradiotherapy (CCRT) significantly improved progression-free survival (PFS) compared to placebo with CCRT in patients with high-risk, locally advanced cervical cancer (LACC).
The second interim analysis of the study now reports overall survival (OS) results, reinforcing the efficacy of this treatment approach. The study included patients newly diagnosed with high-risk LACC and participants were randomised 1:1 to receive 5 cycles of either pembrolizumab 200 mg or placebo every three weeks in combination with CCRT. This protocol was followed by 15 cycles of pembrolizumab 400 mg or placebo every six weeks.
The CCRT regimen included 5–6 weekly cycles of cisplatin at 40mg/m², along with external beam radiotherapy, followed by brachytherapy. Patients were stratified based on external beam radiotherapy type, cancer stage at screening (IB2-IIB versus III-IVA), and total planned radiotherapy dose (<70 Gy versus ≥70 Gy).
Among 1060 patients, 529 were assigned to pembrolizumab with CCRT, and 531 to placebo with CCRT. As of January 8, 2024, with a median follow-up of 29.9 months (range: 12.8–43.0 months), pembrolizumab + CCRT significantly improved OS. The 36-month OS rate was 82.6% in the pembrolizumab group compared to 74.8% in the placebo group. The median OS was not reached in either group, with a hazard ratio of 0.67 (95% CI: 0.50–0.90; P=0.0040), indicating a strong survival advantage with pembrolizumab.
This benefit was consistent across subgroups, with a hazard ratio of 0.89 (95% CI: 0.55–1.44) in FIGO stages IB2-IIB and 0.57 (95% CI: 0.39–0.83) in stages III-IVA. Safety was manageable, with grade ≥3 treatment-related adverse events in 69.1% of patients on pembrolizumab versus 61.3% on placebo.
These findings confirm that pembrolizumab with CCRT offers a statistically significant, clinically meaningful improvement in survival for patients with high-risk LACC and could be considered as a new standard of care.
Katie Wright, EMJ
Reference
Lorusso D et al. Pembrolizumab plus chemoradiotherapy for high-risk locally advanced cervical cancer: Overall survival results from the randomized, double-blind, phase III ENGOT-cx11/GOG-3047/KEYNOTE-A18 study. Abstract 7090. ESMO Annual Meeting, 13-17 September, 2024.
