KEY TAKEAWAYS
- The phase 3 trial aimed to evaluate OS with pembro plus CCRT in patients with high-risk LACC.
- The primary endpoints were to determine PFS and OS.
- Researchers noted significant OS improvement with pembro plus CCRT, endorsing it as a new standard of care.
The phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study (NCT04221945) first interim analysis demonstrated that pembrolizumab (pembro) plus concurrent chemoradiotherapy (CCRT) significantly improved progression-free survival (PFS) compared to placebo (PBO) plus CCRT in patients with high-risk locally advanced cervical cancer (LACC). Following this, the US FDA approved pembro + CCRT for FIGO 2014 Stage III-IVA cervical cancer.
Domenica Lorusso and the team aimed to assess the impact of pembro plus CCRT on overall survival in this patient population from the second interim analysis.
They performed an inclusive analysis involving patients with newly diagnosed, previously untreated, high-risk LACC (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA regardless of lymph node status). Patients were randomized 1:1 to receive either 5 cycles of pembrolizumab 200 mg or PBO every 3 weeks (Q3W) plus CCRT, followed by 15 cycles of pembrolizumab 400 mg or PBO every 6 weeks (Q6W). CCRT consisted of 5 cycles (with an optional 6th dose) of cisplatin 40 mg/m² weekly, combined with external beam radiotherapy (EBRT) and brachytherapy.
Patients were stratified by planned EBRT type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), stage at screening (IB2-IIB vs III-IVA), and planned total radiotherapy dose (<70 Gy vs ≥70 Gy [EQ2D]). The primary endpoints were PFS per RECIST v1.1 by the investigator and OS.
About 1060 patients were randomized to pembro + CCRT (n=529) or PBO + CCRT (n=531). As of the January 8, 2024, data cutoff, the median follow-up was 29.9 months (range, 12.8-43.0). Pembro + CCRT demonstrated a statistically significant improvement in OS compared to PBO + CCRT. The 36-month OS rate was 82.6% with pembro + CCRT versus 74.8% with PBO + CCRT; median OS was not reached in either group (HR=0.67 [95% CI, 0.50-0.90]; P=0.0040).
The benefit of pembro + CCRT was generally consistent across all prespecified subgroups, including FIGO stages IB2-IIB (HR=0.89 [95% CI, 0.55-1.44]) and III-IVA (HR=0.57 [95% CI, 0.39-0.83]). Grade ≥3 treatment-related adverse events (TRAEs) occurred in 69.1% of the pembro + CCRT group and 61.3% of the PBO + CCRT group.
The study concluded that pembro + CCRT showed a statistically significant and clinically meaningful improvement in OS compared to PBO + CCRT in patients with high-risk LACC, with a manageable safety profile. These findings support the use of pembro + CCRT as a new standard of care for this patient population.
The trial was sponsored by the Merck Sharp & Dohme LLC.
Source: https://cslide.ctimeetingtech.com/esmo2024/attendee/confcal/show/session/101
Clinical Trial: https://clinicaltrials.gov/study/NCT04221945
Lorusso D, Xiang Y, Hasegawa K, et al. (2024). “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.” Presented at ESMO 2024 (Abstract 709O).
