The data of the KEYNOTE-A18 study disclosed at the Presidential Symposium I of the 2024 ESMO Congress shows that the overall survival (OS) of newly diagnosed patients with locally advanced cervical cancer who received pembrolizumab and concurrent chemoradiotherapy (CRT) is significantly improved (abstract number 709O). The 36-month OS rate of pembrolizumab + concurrent CRT treatment is 82.6%, and the 36-month OS rate of placebo + concurrent CRT treatment is 74.8% (hazard ratio [HR]=0.67; 95% confidence interval [CI]: 0.50–0.90; P=0.0040). The median OS has not been reached in both treatment groups. The survival benefit is consistent in all prespecified subgroups. At a median follow-up of 29.9 months, the 36-month progression-free survival (PFS) rates of the pembrolizumab group and the placebo group are 69.3% and 56.9%, respectively, and the median PFS is still NR (HR=0.68; 95% CI: 0.56-0.84). The incidences of grade ≥3 treatment-related adverse events in the two treatment groups are 69.1% and 61.3%, respectively. Quality of life (QOL) is not affected. At week 36, using the EORTC QLQ-C30 quality of life index questionnaire, no clinically significant differences between groups are reported.

Dr. Domenica Lorusso from Humanitas Hospital San Pio X ,Humanitas University in Milan, Italy, reported the results of the second interim analysis of the KEYNOTE-A18 at ESMO 2024 and further interpreted the impact of research data on clinical practice in an interview with Oncology Frontier.

Oncology Frontier: The phase III KEYNOTE-A18 study explored the OS data of patients with high-risk locally advanced cervical cancer treated with pembrolizumab combined with chemoradiotherapy. How will these new data affect the clinical treatment of patients with high-risk locally advanced cervical cancer?

Dr. Lorusso: KEYNOTE-A18 is a randomized placebo-controlled phase III trial evaluating the role of pembrolizumab i combination with chemoradiation in locally advanced high-risk cervical cancer. The trial is a global trial and enrolled >1000 patients across the world from 30 countries and 176 centers. The trial reported a significant three-year increase in progression-free survival with a hazard ratio of 0.68 and a significant three-year increase in overall survival with a hazard ratio of 0.67. The toxicity profile of the combination was really manageable. We were surprised at how manageable this pembrolizumab combination with modern and high quality radiotherapy was. The incidence, type and severity of adverse events were very similar between the two treatment arms. The most frequently reported toxicities were anemia, nausea and diarrhea, but in terms of intensity, very similar between the two treatment arms. Patients treated with pembrolizumab had immune-related adverse events. Hypothyroidism was reported in about 40% of cases, but it was mainly grade 1/2 and managed with hormone replacement therapy. In addition, quality of life was not jeopardized when pembrolizumab was combined with chemoradiation. So based on all this information, we consider this to be a new standard-of-care in patients with locally advanced high-risk cervical cancer.

I think based on these data, we can consider concurrent chemoradiation plus immunotherapy as the new standard-of-care. In the last 25 years, we have not had any change in the standard-of-care in cervical cancer. The only great impact was related to the modern radiotherapy that reduced toxicity, while increasing local control and overall survival. On top of this modern standard of radiotherapy, the addition of pembrolizumab and the extra 8% overall survival at three years, we are really convinced this is the new standard-of-care.