Data confirm survival benefit of pembrolizumab regimen for advanced cervical cancer
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Key takeaways:
- Final OS results showed the anti-PD-1 therapy significantly reduced risk for death across subgroups when added to chemotherapy, with or without bevacizumab.
- The regimen also had a manageable safety profile.
The addition of pembrolizumab to chemotherapy, with or without bevacizumab, significantly extended OS and PFS among women with persistent, recurrent or metastatic cervical cancer, according to data from the KEYNOTE-826 study.
Final OS results of the randomized, phase 3 study, presented during a press conference ahead of ASCO Annual Meeting, further support the pembrolizumab (Keytruda, Merck) regimen as first-line therapy for this patient population.
Rationale and methods
“In 2009, the standard treatment for these patients consisted of chemotherapy with platinum and taxane, either cisplatin or carboplatin, and paclitaxel. It wasn’t until 2014 that we saw the approval of bevacizumab [Avastin, Genentech], the first-ever targeted therapy in the gynecologic cancer space,” Bradley J. Monk, MD, FACS, FACOG, co-director of the Gynecologic Oncology Group, researcher at HonorHealth Research Institute, and professor at University of Arizona College of Medicine and Creighton University School of Medicine, told Healio. “Seven years later, KEYNOTE-826 was presented at ESMO and simultaneously published in The New England Journal of Medicine, which led to FDA approval on Oct. 13, 2021. However, that publication, presentation and subsequent FDA approval were all based on preliminary interim analysis results.”
As Healio previously reported, the KEYNOTE-826 trial included 617 women with persistent, recurrent or metastatic cervical cancer. Among them, 548 had a PD-L1 combined positive score (CPS) of 1 or greater and 317 had a PD-L1 CPS of 10 or greater.
Researchers randomly assigned 308 women (median age, 51 years) to 200 mg pembrolizumab and 309 women (median age, 50 years) to placebo every 3 weeks for up to 35 cycles.
All women also received chemotherapy with paclitaxel and cisplatin or carboplatin, and 63.6% in the pembrolizumab group and 62.5% in the placebo group also received bevacizumab. Researchers grouped women according to metastatic status at diagnosis, planned use of bevacizumab and PD-L1 CPS.
During the press conference, Monk presented the protocol-specific final OS results with median follow-up of 39.1 months.
Findings
Results showed median OS of 26.4 months (95% CI, 21.3-32.5) with the pembrolizumab regimen vs. 16.8 months (95% CI, 14.6-19.4) with placebo among the all-comer population (HR = 0.63; 95% CI, 0.52-0.77).
Researchers observed an even greater OS benefit with pembrolizumab among women with a PD-L1 CPS of 1 or higher (median, 28.6 months vs. 16.5 months; HR = 0.6; 95% CI, 0.49-0.74) and a PD-L1 CPS of 10 or higher (29.6 months vs. 17.4 months; HR = 0.58; 95% CI, 0.44-0.78).
Median PFS was 10.4 months with pembrolizumab vs. 8.2 months with placebo among the all-comer population (HR = 0.61; 95% CI, 0.5-0.74).
The combination of pembrolizumab and chemotherapy with or without bevacizumab exhibited a manageable safety profile, with no new safety signals, Monk said.
“With more than 3 years of follow-up, we can now say that we know the exact benefit of pembrolizumab and with precision,” Monk said. “In addition, in April 2023, we published patient-reported outcomes that showed that not only are these patients living longer, but they are doing so without feeling sicker. The addition of pembrolizumab to chemotherapy, with or without bevacizumab, was not associated with a decrement in quality of life and we now know that these women are living 12.1 months longer on average. These are transformational results.”
Implications
These long-term follow-up results support the use of pembrolizumab with chemotherapy, with or without bevacizumab, as a new standard of care for first-line treatment of this patient population, Monk told Healio.
“We will continue to build upon treatment success so that our patients can remain alive and well,” he said. “KEYNOTE-826 changed the world. We have now enrolled patients on the A-18 trial, which we are excited about. Our hope is to evolve the treatment strategy by earlier lines of therapy and with novel agent combinations.”
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Monk BJ, et al. Abstract 5500. Presented at: ASCO Annual Meeting; June 2-6, 2023; Chicago.
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