Phase 3 KEYNOTE-A18 Trial Data Are ‘Practice Changing’ for Cervical Cancer

Overall survival (OS) and progression-free survival (PFS) findings from the phase 3 KEYNOTE-A18 study (NCT04221945), assessing pembrolizumab (Keytruda) plus chemoradiotherapy, may prove to be “practice-changing” for those with newly diagnosed, previously untreated, high-risk, locally advanced cervical cancer, according to Domenica Lorusso, MD, PhD.

Lorusso, a gynecologic oncologist at Fondazione IRCCS National Cancer Institute of Milan, spoke to the significance of the study’s findings and provided guidance on how practitioners can feel confident about the regimen’s safety and efficacy. The study’s findings were presented at the 2023 Annual Global Meeting of the International Gynecologic Cancer Society (IGCS).

Transcript:

This is a practice-changing trial. We were looking for OS but also PFS in a curative setting. It's also important to evaluate [these end points] because in KEYNOTE-A18, there will be patients who receive immunotherapy after progression because the KEYNOTE-826 trial [NCT03635567…has led to] approval [of pembrolizumab] all over the world. We have to take immunotherapy after progression into consideration; we have to take tisotumab vedotin-tftv [Tivdak] into consideration now. We have a lot of drugs that are reported to increase OS in cervical cancer. The availability of drug efficacy post-progression may make it more difficult to evaluate OS in the locally advanced setting. We are collecting data and are confident of that.

I really believe this is a practice-changing trial. One very important point that I want to underline is that if you want to be very confident that pembrolizumab is adding something in terms of benefit to chemoradiation, you have to be very confident in the quality of the chemoradiation that you're giving. Otherwise, you cannot be sure that what you are adding can counterbalance low-quality radiotherapy. When we designed the trial, we took particular care of the quality of radiotherapy that the patient had to receive in our trial. That's the reason why we have quality control of the center before enrollment; every single treatment plan was reviewed.

Now we are very confident of the quality of our radiotherapy. The median total cervical dose was 87, which is in the range of the high-quality radiotherapy. More than 90% of our patients receive intensity modulated radiation therapy [IMRT] and volumetric-modulated arc therapy [VMAT], which are standard radiotherapy [options]. In the context of this good quality radiotherapy and this standard radiotherapy, we are much more confident of the 30% reduction in the risk of progression that pembrolizumab provides. That's important when we have to evaluate a new treatment. Thanks to this high-quality radiotherapy, I'm strongly convinced we did not see additional toxicity; this modern confirmational, volumetric radiotherapy technique avoids and spares the organs. That's the reason why the toxicity profile was very good.

Reference

Lorusso D, Xiang Y, Hasegawa K, et al. ENGOT-cx11/GOG-3047/KEYNOTE-A18: a randomized, double-blind, phase 3 study of pembrolizumab plus chemoradiotherapy for high-risk locally advanced cervical cancer. Presented at 2023 Annual Global Meeting of the International Gynecologic Cancer Society; November 5-7, 2023; Seoul, South Korea; abstract SE004/1614.