Dr Duska on Pembrolizumab Plus Chemoradiotherapy in Cervical Cancer

“Even with modern radiation and chemotherapy, the relapse rate [for patients with high-risk cervical cancer] can be as high as 50%. We really haven’t had any changes in therapy since 1999.”

Linda R. Duska, MD, MPH, a gynecologic oncologist and professor in the Department of Obstetrics and Gynecology, Gynecological Oncology Division, at the University of Virginia (UVA) Health; as well as the associate dean for Clinical Research at UVA School of Medicine, discussed the background of the phase 3 KEYNOTE-A18 trial (NCT04221945).

KEYNOTE-A18 examined pembrolizumab (Keytruda) plus chemoradiotherapy followed by pembrolizumab monotherapy for the treatment of patients with newly diagnosed, high-risk cervical cancer. Patients with locally advanced cervical cancer have limited treatment options and the standard of care for these patients has remained the same for many years, underscoring the need for the development of new therapies in clinical trials, Duska began.

Findings from the first interim analysis of KEYNOTE-A18 showed that the study met its primary end point, displaying a statistically significant improvement in progression-free survival with pembrolizumab plus chemoradiotherapy followed by pembrolizumab monotherapy vs chemoradiotherapy plus placebo, Duska explained. Based on these data, the FDA approved pembrolizumab in combination with chemoradiotherapy for the treatment of patients with FIGO 2014 stage III to IVA cervical cancer, in January 2024. During the 2025 SGO Annual Meeting on Women’s Cancer, the study authors presented data from the second interim analysis of KEYNOTE-A18, including overall survival (OS) and time to second progression findings, Duska noted.

These updated findings showed that the 36-month PFS rates were 62.7% and 54.5% with the pembrolizumab vs placebo arms, respectively (HR, 0.68; 95% CI, 0.65-0.84). The 36-month OS rates were 82.6% (95% CI, 78.4%) and 74.8% (95% CI, 70.1%-78.8%), respectively. The HR for OS was 0.67 (95% CI, 0.50-0.90; P = .0040) in favor of the pembrolizumab arm.