The addition of pembrolizumab to chemoradiotherapy demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) compared to placebo plus chemoradiotherapy in patients with high-risk, locally advanced cervical cancer, according to a second interim analysis from the phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study.

At the first interim analysis, pembrolizumab plus chemoradiotherapy showed an improvement in progression-free survival (PFS) vs placebo and chemoradiotherapy in patients with high-risk locally advanced cervical cancer, leading to the US FDA approval of this combination for patients with FIGO 2014 Stage III-IVA cervical cancer.

The OS results from the second interim analysis were presented by Domenica Lorusso, MD, PhD, Fondazione IRCCS National Cancer Institute of Milan, Italy, lead investigator of the trial in a Presidential Symposium at the 2024 ESMO Congress in Barcelona, Spain.

The trial enrolled patients with newly diagnosed, previously untreated, high-risk locally advanced cervical cancer and FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA regardless of lymph node status.

Patients were randomized in a 1:1 ratio to the pembrolizumab arm or the placebo arm. 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 end points of the trial are PFS per RECIST v1.1 by investigator and OS.

Overall, 1060 patients were enrolled and randomized to the pembrolizumab arm (n = 529) or placebo arm (n = 531). At this analysis, and a data cutoff date of January 8, 2024, median follow-up was 29.9 months (range, 12.8 to 43).

The 36-month OS rate was 82.6% with pembrolizumab vs 74.8% with placebo. Median OS was not reached in either group (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.50 to 0.90; P = .0040). Researchers noted that the benefit of pembrolizumab was consistent across all prespecified subgroups, including FIGO stages IB2-IIB (HR, 0.89; 95% CI, 0.55 to 1.44) and III-IVA (HR, 0.57; 95% CI, 0.39 to 0.83).

Grade ≥3 treatment-related adverse events were reported in 69.1% of patients in the pembrolizumab arm and 61.3% of patients in the placebo arm.

In conclusion, pembrolizumab plus chemoradiotherapy showed a statistically significant and clinically meaningful improvement in OS vs placebo plus chemoradiotherapy in patients with high-risk locally advanced cervical cancer and had a manageable safety profile.

“These data provide further support for pembrolizumab plus chemoradiotherapy as a new standard of care for this population,” concluded Dr Lorusso.

Source:

Lorusso D, Xiang Y, Hasegawa K, 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. Presented at 2024 ESMO Congress. September 13-17, 2024. Abstract 709O