Pembrolizumab plus chemoradiotherapy shows clinically meaningful improvement in PFS for locally advanced cervical cancer

Prof Domenica Lorusso - Fondazione IRCCS National Cancer Institute, Milan, Italy

Since 1999 chemoradiation in combination with brachytherapy has been identified as the standard of care for locally advanced cervical cancer but several preclinical and clinical data suggest that when we combine immunotherapy plus chemoradiation we can enhance the efficacy of chemoradiation. So, based on this rationale, we tried to explore if the combination of pembrolizumab plus chemoradiation may enhance the efficacy of chemoradiation in locally advanced high-risk cervical cancer.

KEYNOTE-A18 is a randomised phase III trial, a global randomised phase III trial, enrolling 1,060 patients in 176 centres in 30 countries. Patients with stage 1b, 2, 2b and node-positive or stage 3 and 4a regardless of lymph node status were randomised to receive concurrent chemoradiation plus brachytherapy in combination and maintenance with pembrolizumab for one year or the same treatment plus placebo. The trail has two primary endpoints: progression-free and overall survival. Here we reported the final progression-free survival and the interim analysis for overall survival.

A statistically significant and clinically meaningful decrease in the risk of progression was reported for patients treated with pembrolizumab in combination with chemoradiation. In particular, the hazard ratio was 0.70, suggesting a 30% reduction in the risk of progression. Overall survival data at this interim analysis are not mature, referring to less than 43% of events, but a trend towards an increase in overall survival was reported with a hazard ratio of 0.73 that did not reach the prespecified criteria for significance but it seems very, very promising.

In addition, the combination of pembrolizumab plus chemoradiation is feasible with only a few additional grade 3 and 4 adverse events. All the patients continued treatment in the pembrolizumab arm and no deterioration in quality of life was reported. Honestly, I think that this data paves the way for a new treatment in locally advanced cervical cancer.