Pembrolizumab Plus Chemotherapy Regimen Yields Clinically Positive Outcomes for Treatment of Locally Advanced Cervical Cancer
New approach confirms the effectiveness of a new standard of care.
Patients with high-risk, locally advanced cervical cancer (LACC) now have more reasons to be excited about their clinicians’ choice to add immunotherapy in their primary treatment, with most recent data showing improved overall survival (OS). The late-breaking abstract, “Pembrolizumab plus chemoradiotherapy for high-risk locally advanced cervical cancer: overall survival and progression-free survival 2 (PFS2) results from the randomized, double-blind, phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study” offers compelling data to support the addition of pembrolizumab to concurrent chemoradiotherapy (CCRT) in patients with high risk LACC.
Linda Duska, MD, MPH, professor of obstetrics and gynecology at the University of Virginia School of Medicine in Charlottesville was the U.S. national principal investigator (PI) for the international study that analyzed the effect of combining pembrolizumab with CCRT, followed by pembrolizumab maintenance. The phase 3 findings, she said, offer data regarding progression-free survival 2 (PFS2), which is defined as time from initiation of new anticancer therapy to second disease progression or death from any cause. The study’s results from the first analysis resulted in a new standard of care for patients with high-risk LACC. The current analysis supports the OS data first reported at the European Society for Medical Oncology (ESMO) Annual Meeting in 2024 and provides new data regarding the reduced risk of a second progression following first-line therapy.
“The data strongly support the conclusion that patients who meet the eligibility criteria of this study should be offered pembrolizumab with CRT followed by maintenance pembrolizumab for the optimal clinical outcome,” Dr. Duska said.
Researchers followed 1,060 patients with newly diagnosed, previously untreated, high-risk LACC. The double-blind study randomized subjects between the pembrolizumab plus CCRT (experimental) arm and the placebo plus CCRT group, followed by pembrolizumab or placebo maintenance therapy. The study’s two primary endpoints were PFS and OS. Secondary endpoints included the time from randomization to subsequent disease progression after initiation of new anticancer therapy or death from any cause (PFS2), patient reported outcomes, and safety.
The results, which were presented earlier today, discussed at SGO 2025 are from the second planned interim analysis. The combination of pembrolizumab and CCRT showed a statistically significant improvement in OS compared to the placebo group. The 36-month OS rate was 82.6% for the pembrolizumab group, compared to 74.8% for the placebo group, with a hazard ratio (HR) for OS of 0.67, indicating a 33% reduction in the risk of death for patients receiving the experimental regimen.
The study also revealed improvement in PFS2, with events occurring in 15.3% of patients in the pembrolizumab group versus 24.3% in the placebo group with a hazard ratio of 0.60. Findings will change the therapeutic direction in the future, Dr. Duska said.
“Our results confirm the value of this regimen to patients with high risk LACC,” she said. “These data support pembrolizumab plus CCRT as the new standard of care for patients with newly diagnosed, previously untreated, high risk LACC and as an appropriate control arm in future clinical trials.”
Recognizing that chemoradiation in this setting is a difficult regimen for patients, the experimental arm did have a higher incidence of adverse events. Dr. Duska said the incidence of grade 3 or higher treatment-related, adverse events was higher in the pembrolizumab group (69.1%) compared to the placebo group (61.3%). However, all side effects were manageable.
Based on this study, pembrolizumab plus CCRT was approved in the United States and Europe for patients with International Federation of Gynecology and Obstetrics (FIGO) 2014 stage III-IVA cervical cancer.
“While the findings from this study are practice-changing, further work is needed to ensure equitable access to this new standard of care in a population that is commonly impacted by well-defined social determinants of health,” she said.
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