Pembrolizumab Combined with CCRT Shows Promise in Cervical Cancer

In a significant advancement for cancer treatment, the final results of the phase 3 ENGOT-cx11/GOG-3407/KEYNOTE-A18 study have demonstrated that pembrolizumab, when used in conjunction with concurrent chemoradiation therapy (CCRT), could potentially become the standard of care for patients suffering from high-risk locally advanced cervical cancer. These findings were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, showcasing a sustained survival benefit for patients receiving this innovative treatment regimen.

The study, led by Dr. Linda R. Duska, MD, MPH, from the University of Virginia Health in Charlottesville, VA, involved 1,060 patients diagnosed with high-risk locally advanced cervical cancer, as defined by FIGO 2014 guidelines. This patient cohort included those with stage IB2 to IIB, node-positive disease, as well as stages III to IVA, regardless of lymph node involvement. Participants were randomly assigned to either receive 200 mg of pembrolizumab or placebo every three weeks for five cycles, followed by 400 mg every six weeks for an additional 15 cycles, in conjunction with standard chemoradiotherapy (CRT).

At a median follow-up of 41.9 months, the study revealed a hazard ratio for progression-free survival (PFS) of 0.72 (95% CI, 0.59-0.87), indicating a statistically significant improvement in PFS for those treated with pembrolizumab compared to the placebo group. Specifically, the 24-month PFS rates were 70.6% for the pembrolizumab arm versus 59.7% for the placebo arm, while the 36-month PFS rates were 64.3% and 55.6%, respectively. Furthermore, the overall survival (OS) rates also favored the pembrolizumab group, with a hazard ratio of 0.73 (95% CI, 0.57-0.94).

Dr. Duska emphasized the importance of these results, stating, "These data are consistent with the prior interim analyses and provide further support for pembrolizumab plus CCRT as the new standard of care for this population." The study's design included two primary endpoints: PFS and OS, which were analyzed hierarchically, first assessing PFS before recycling alpha to OS if PFS was significant.

The safety profile of the treatment was consistent with known effects of the individual agents, with treatment-related adverse effects (TRAEs) occurring in nearly all patients (97.0% in the pembrolizumab arm vs. 96.8% in the placebo arm). Importantly, the data did not reveal any new safety signals with prolonged follow-up, reinforcing the treatment's viability.

In terms of subgroup analyses, outcomes were favorable across various demographics, though patients aged 65 years and older did not experience the same benefits as younger cohorts. Notably, 33.3% of patients received post-progression therapy, which is known to impact overall survival outcomes.

The findings from this study not only highlight the potential of pembrolizumab in treating high-risk cervical cancer but also underscore the ongoing need for innovative treatment strategies in oncology. As researchers continue to explore the implications of these results, the medical community is poised to reassess treatment guidelines for cervical cancer, potentially incorporating pembrolizumab and CCRT as a new standard of care.

This study marks a pivotal moment in cervical cancer treatment, offering hope to patients and healthcare providers alike, and driving further research into the efficacy of immunotherapy in conjunction with traditional treatments. With ongoing investigations and clinical trials, the future of cervical cancer management is evolving, presenting new opportunities for improved patient outcomes.