The results from the KEYNOTE-A18 study, presented at the ESMO Congress 2023, reveal that the combination of pembrolizumab and concurrent chemoradiotherapy (CCRT) significantly improves progression-free survival (PFS) in high-risk, locally advanced cervical cancer. The study’s co-primary endpoint, PFS, showed a notable improvement for patients receiving pembrolizumab and CCRT versus those receiving placebo and CCRT, with a hazard ratio (HR) of 0.70 (95% CI 0.55–0.89; p=0.0020).
While overall survival (OS) data are still immature, there was a favorable trend in the pembrolizumab arm (HR 0.73; 95% CI 0.49–1.07). Additionally, the combination was found to have a manageable safety profile. Prof. Bradley J. Monk, from the University of Arizona College of Medicine and Creighton University School of Medicine, described the results as "very exciting" and emphasized that this is the first positive study in locally advanced cervical cancer since 1999. He suggested that checkpoint inhibitors could be the "next frontier" in treating this disease.
The findings contrast with the disappointing results of the phase III CALLA trial, which evaluated the PD-L1 inhibitor durvalumab in the same patient population. Prof. Monk speculated that differences in sample size or the higher-risk population in KEYNOTE-A18 might explain the positive results, along with potential differences in the mechanisms of action between PD-1 inhibitors like pembrolizumab and PD-L1 inhibitors like durvalumab. Additionally, the results of the GCIG INTERLACE trial, which investigates induction chemotherapy before CCRT, are eagerly awaited and will be presented at the ESMO Congress 2023.
Prof. Monk concluded by underscoring the growing role of checkpoint inhibitors in cervical cancer treatment. He noted their effectiveness as second-line and first-line therapies for metastatic, recurrent, or persistent cervical cancer, as well as their potential when combined with chemotherapy and radiotherapy in locally advanced cases. Looking ahead, he stressed the need for novel therapies for patients progressing on standard treatments. Antibody-drug conjugates targeting molecules like tissue factor or HER2 expressed on cervical cancers represent a promising strategy, offering hope for patients with disease progression.