Adding pembrolizumab to chemoradiotherapy improves outcomes in high-risk cervical cancer
Key takeaways:
- The addition of pembrolizumab to chemoradiotherapy improved PFS and OS for women with high-risk, locally advanced cervical cancer.
- The safety profile appeared consistent with that of the individual therapies.
The addition of pembrolizumab to chemoradiotherapy improved survival outcomes for women with high-risk, locally advanced cervical cancer, according to data presented at Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.
Study results showed “statistically significant and clinically meaningful improvements” to PFS and OS, according to researchers.
“These data support the use of this combination regimen as the new standard of care for patients with high-risk, locally advanced cervical cancer and as a potential appropriate control arm in future clinical trials,” Linda R. Duska, MD, gynecologic oncologist at University of Virginia School of Medicine, said during a presentation.
Pembrolizumab (Keytruda, Merck) is an anti-PD-1 therapy.
Healio previously reported that the FDA approved this combination for the treatment of certain women with stage III to stage IVA cervical cancer, making it the third approved cervical cancer indication for pembrolizumab at that time.
The agency based the decision on data from the randomized phase 3 KEYNOTE-A18 trial.
Healio also previously reported data from a prespecified interim analysis from this trial, which showed a favorable trend in OS and PFS.
At the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer, Duska presented OS and PFS2 data from the ENGOT-cx11/GOG-3047/KEYNOTE-A18 study.
The study included 1,060 treatment-naive women with FIGO 2014 stage IB2 to IIB (node-positive disease) or FIGO 2014 stage III to IVA (node-positive or node-negative disease).
Patients received 40 mg/m2 cisplatin once a week for five cycles in combination with external beam radiation therapy followed by brachytherapy, plus either 200 mg pembrolizumab (n = 529; median age, 49 years; 48% white) or placebo (n = 531; median age, 50 years; 49.7% white) once every 3 weeks for five cycles.
Patients then received either 400 mg pembrolizumab (investigative cohort) or placebo (control cohort) once every 6 weeks for 15 cycles.
PFS and OS served as primary endpoints. PFS2 — defined as time from randomization to disease progression after initiation of new anticancer
therapy or death due to any cause — served as a secondary endpoint.
At second interim analysis, patients who received the pembrolizumab-led combination exhibited better PFS at 3 years (HR = 0.68; 95% CI, 0.56-0.84) and OS at 3 years (HR = 0.67; 95% CI, 0.5-0.9).
Patients in this cohort also demonstrated better PFS2 (HR = 0.6; 95% CI, 0.46-0.8).
Data showed that more patients who received pembrolizumab vs. placebo experienced grade 3 or higher treatment-related adverse events (69.1% vs 61.3%). The pembrolizumab cohort also had a higher proportion of patients with treatment-related adverse events that led to discontinuation of any treatment (18.8% vs 13%).
Despite this, researchers described the safety profile of pembrolizumab combined with concurrent chemoradiotherapy as manageable and consistent with known safety profiles of the individual therapies. They did not identify new safety signals.
Perspective
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Cervical cancer is preventable thanks to HPV vaccination, which has been available for over 15 years. Global coverage remains low, however, with an estimated 27% of girls receiving the first dose of HPV vaccine. Many countries do not include HPV vaccine in their national vaccination programs.
In 2023, approximately 77% of adolescents in the U.S. received only one dose, and 61% received the full series.
Hence, this remains a global issue, with over 660,000 women diagnosed with cervical cancer worldwide in 2022. In the United States, we will have over 13,000 women diagnosed with this disease in 2025.
Locally advanced cervical cancer treatment had not changed since the use of weekly cisplatin and external beam radiation, followed by intracavitary or interstitial brachytherapy in 1999.
Then results of KEYNOTE-A18 showed improved progression-free survival and overall survival with the use of pembrolizumab, which led to FDA approval for patients with stage III or IVA disease. The curves still favor pembrolizumab at all stages, without any new adverse events or safety concerns, making this the new standard of care for patients with high-risk locally advanced cervical cancer.
I believe we have really moved the needle by … changing care for women with locally advanced cervical cancer with the inclusion of pembrolizumab. With these advancements, however, we must make sure all patients with cervical cancer have equitable benefit from these advances, both here in the U.S. and globally.
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Duska LR, et al. Pembrolizumab plus chemoradiotherapy for high-risk locally advanced cervical cancer: Overall survival and progression-free survival 2 results from the randomized, double-blind, phase III ENGOT-cx11/GOG-3047/KEYNOTE-A18 Study. Presented at: SGO Annual Meeting on Women’s Cancer; March 14-17, 2025; Seattle.