Pembrolizumab Sets New Standard in Advanced Cervical Cancer Care
Cervical cancer prevention advances with new immunotherapy findings, addressing disparities and improving outcomes for underserved women globally.
Microscopic, photorealistic image of cervical cancer cells - Generated with Adobe Firefly
Cervical cancer, a leading cause of cancer-related death among women globally, is largely preventable through human papillomavirus (HPV) vaccination and screening. Yet significant disparities in incidence and survival persist, particularly in underserved communities and rural areas, highlighting a critical global public health challenge. At the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, Linda R. Duska, MD, MPH, presented the final analysis of the pivotal phase 3 KEYNOTE-A18 study(NCT04221945), which has redefined the standard of care for high-risk locally advanced cervical cancer.
Duska, a gynecologic oncologist at University of Virginia Health and, a passionate advocate for cervical cancer prevention and equitable care, emphasized the urgent need to address systemic barriers to screening and vaccination worldwide. In the US, she noted, "we have diverse racial inequities with respect to cervical cancer [in] incidence and survivorship, but we also have inequities with respect to social determinants of health." This disease disproportionately affects economically disadvantaged women, those without health insurance, and women in rural areas, including regions like Appalachia, where Duska is located and where incidence rates are alarmingly high.
Despite advancements in chemoradiotherapy techniques, a significant unmet need has remained: improving outcomes for women with locally advanced cervical cancer who are not cured by current treatments. The KEYNOTE-A18 study sought to address this by investigating whether adding pembrolizumab (Keytruda) immunotherapy to modern radiation therapy could enhance progression-free survival (PFS) and overall survival (OS).
A Landmark Global Trial Amidst a Pandemic
KEYNOTE-A18 was a randomized, double-blind, placebo-controlled international trial that accrued over 1000 patients between 2020 and 2022, a period marked by the COVID-19 pandemic. The study focused on women with high-risk locally advanced cervical cancer, defined by FIGO 2014 staging as IB to II with positive nodes or stage III to IVA.
Patients were randomly assigned 1:1 to receive either standard chemoradiation plus placebo, followed by placebo maintenance, or standard chemoradiation with 5 cycles of pembrolizumab, followed by pembrolizumab maintenance. The primary end points were PFS and OS.
"At the time of the first interim analysis...the study met the progression-free survival end point, which was really exciting," Duska said. The hazard ratio was statistically significant at 0.7. A year later, at the second interim analysis, the trial also met its OS end point with a hazard ratio of 0.68.
Final Analysis Confirms Efficacy and Safety
The ASCO 2025 presentation marked the final analysis, with a median follow-up of 42 months. The results confirmed the earlier findings: "The progression-free survival and overall survival numbers that we saw in the first 2 interim analysis held up. They were confirmed," Duska said. The PFS curves remained separated at 24 and 36 months, demonstrating sustained benefit. Crucially, the long-term follow-up revealed no new safety signals, indicating that adding pembrolizumab to chemoradiation is safe and manageable.
Key Takeaways for Community Oncologists
For community oncologists, Duska emphasized the immediate impact of these findings: "First of all, in this group of patients, this is the new standard of care." However, she stressed that the success of this regimen is highly dependent on the quality of radiation therapy.
"We were vigilant about making sure that patients got high-quality radiation," she explained, highlighting the importance of modern techniques, universal brachytherapy (ideally high-dose-rate), and timely completion of radiation within 56 days. The median of 5 cycles of cisplatin during radiation also reflects adherence to standard of care.
Duska urged practitioners to recognize the substantial support these patients need due to the toxicity of chemoradiation. "These patients need a lot of support. They need to be seen frequently; their nausea, their dehydration, etc, need to be managed." Ensuring high-quality chemoradiation alongside immunotherapy is paramount to maximizing patient outcomes.
Future Directions and Persistent Advocacy
While the KEYNOTE-A18 study provides definitive answers, Duska noted that much more data are yet to be explored. Future analyses will delve into prespecified subgroups, markers for recurrence, and quality of life.
Personally, Duska is keen to understand the optimal sequencing of checkpoint inhibitors with radiation—whether concurrent therapy, maintenance, or even neoadjuvant immunotherapy yields the best results.
Ultimately, Duska's message extends beyond clinical trials to a broader call for action. "I am so hopeful that 10 years from now…cervical cancer will not be a problem anymore," she concluded, underscoring the critical need for continued efforts in screening, immunization, education, and advocacy to eliminate this preventable disease.
