PFS, QOL Benefits Seen With Pembrolizumab/Chemoradiation in Cervical Cancer

Findings from the phase 3 KEYNOTE-A18 trial (NCT04221945) support the international “standardization” of pembrolizumab (Keytruda) plus chemoradiotherapy as a treatment for those with advanced cervical cancer, according to Jyoti S. Mayadev, MD.

In a conversation with CancerNetwork^® ahead of the FDA approval of pembrolizumab/chemoradiation in stage III to IVA cervical cancer,¹ Mayadev, a board-certified radiation oncologist and professor of radiation medicine and applied sciences at the University of California, San Diego School of Medicine, highlighted various benefits associated with the regimen that investigators reported in the KEYNOTE-A18 trial. Findings presented at the 2023 European Society for Medical Oncology (ESMO) highlighted a trend in improved overall survival (OS) among those who received pembrolizumab plus chemoradiotherapy compared with patients who were treated with placebo and chemoradiation (HR, 0.73; 95% CI, 0.49-1.07).²

Although there was a progression-free survival (PFS) benefit associated with the experimental regimen, Mayadev stated that this improvement did not extend to all-comers. A subgroup analysis indicated that there was a less pronounced PFS improvement with the pembrolizumab-based regimen in patients with FIGO 2014 stage IB2 to IIB disease (HR, 0.91; 95% CI, 0.63-1.31) compared with those who had stage III to IVA disease (HR, 0.58; 95% CI, 0.42-0.80).¹ Additionally, Mayadev said there was no significant difference in patient-reported outcomes between treatment arms in the KEYNOTE-A18 trial, suggesting that the experimental regimen was tolerable without yielding any negative impacts on quality of life.

Transcript:

In this large KEYNOTE-A18 trial, more than 1060 patients were randomly [assigned] across the globe; there were 156 sites. In general, it led to a standardization across the world on how patients are treated with locally advanced cervical cancer.

In addition to the progression-free survival benefit that was seen, there was a trend in overall survival [with pembrolizumab plus chemoradiation]. This, however, was not seen in all-comers. On the forest plot breakdown at the ESMO presentation, patients with stage IB to IIB—even if they were node positive—did not show significant benefit in progression-free survival. These are things that we’re going to be looking at in terms of who will be included in the FDA approval.

The other things that we learned from ESMO in the KEYNOTE-A18 trial that will translate when we think pembrolizumab will be approved from the FDA is that there was no difference in patient-reported outcomes. The quality-of-life metrics had no difference between the arms, so patients were able to tolerate it well without a detriment in the quality of life.

References

1. FDA approves pembrolizumab with chemoradiotherapy for FIGO 2014 stage III-IVA cervical cancer. News release. January 12, 2024. Accessed January 12, 2024. https://bit.ly/3NZNGPb
2. Lorusso D, Xiang Y, Hasegawa K, et al. Pembrolizumab plus chemoradiotherapy for high-risk locally advanced cervical cancer: a randomized, double-blind, phase III ENGOT-cx11/GOG-3047/ KEYNOTE-A18 study. Ann Oncol. 2023;34(S2):S1279-S1280. doi:10.1016/j.annonc.2023.10.032