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Integrating checkpoint blockade with pembrolizumab (Keytruda) into standard concurrent chemoradiotherapy plus brachytherapy significantly improved progression-free survival in cervical cancer and showed an early trend toward better overall survival (OS) as well, according to trial data presented at the International Gynecologic Cancer Society annual meeting.

Lead author Domenica Lorusso, MD, PhD, of the Catholic University of Rome, discusses why she believes the KEYNOTE-A18 results may prove to be practice-changing and why the quality of the radiotherapy matters in this combination.

Following is a transcript of her remarks:

This is a curative setting. We are looking for overall survival, but also progression-free survival in a curative setting. It's important to evaluate also, because there will be for sure in KEYNOTE-A18 patients that will receive immunotherapy after progression because [with] KEYNOTE-826 [pembrolizumab] has all over the world. So we have to take into consideration immunotherapy after progression. We have to take into consideration tisotumab vedotin [Tivdak]. Now we have a lot of drugs that are reported to increase overall survival in cervical cancer, and potentially in situations like that, the availability of efficacy drug post-progression may make it more difficult to evaluate overall survival in the locally advanced setting. But anyway, we are collecting data and we are confident of that.

So 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] or whichever is adding something in terms of benefit to chemoradiation, you have to be very confident on the quality of chemoradiation that you are giving. Otherwise, you can never be sure that what you are adding simply counterbalances a low quality of radiotherapy. And 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.

And now we are very confident of the quality of our radiotherapy. The median total therapy dose, EQD2 dose is 87 [Gy], which is in the range of the high-quality radiotherapy. More than 90% of our patients receive IMRT [intensity modulated radiation therapy] or VMAT [volumetric modulated arc therapy], which is the standard radiotherapy.

So in the context of this good quality radiotherapy, in the context on 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. And it's important. And thanks to this high-quality radiotherapy, I'm strongly convinced we did not see additional toxicity. Because this modern radiotherapy technique [is] confirmational, volumetric [radiotherapy] avoids and spares the organ. And that's the reason why, also, the toxicity profile was very good.

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