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Interim phase 3 analysis: pembrolizumab plus chemoradiotherapy reported to improve overall survival in high-risk locally advanced cervical cancer

At the second protocol-specified interim analysis of the ENGOT-cx11/GOG-3047/KEYNOTE-A18 study, investigators reported an overall survival benefit with pembrolizumab given with and after chemoradiotherapy versus chemoradiotherapy alone.

  • Domenica Lorusso, MD PhD; Yang Xiang, MD; Kosei Hasegawa, MD PhD; Giovanni Scambia, MD; Manuel Leiva, MD MSc; Pier Ramos-Elias, MD; et al.

  • September 14, 2024

  • The Lancet
  • Volume 404, Issue 10460, Pages 1321–1332
  • 10.1016/S0140-6736(24)01808-7

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Evidence before this study

Novel treatment advances for high-risk locally advanced cervical cancer have been limited for more than two decades, with improvement in local control with modern radiotherapy techniques. We searched PubMed for phase 3 clinical trials published in English between Jan 1, 2013, and Jan 1, 2023, with the terms “locally advanced cervical cancer” and “immunotherapy” and found that no positive study results were reported. Subsequent to the previous disappointing results with chemoradiotherapy-based combination regimens in patients with locally advanced cervical cancer, results from the first protocol-specified interim analysis of the global, randomised, phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study showed that the addition of pembrolizumab to chemoradiotherapy provided a statistically significant and clinically meaningful improvement in progression-free survival as compared with chemoradiotherapy alone in patients with high-risk locally advanced cervical cancer.

Added value of this study

At the second protocol-specified interim analysis of the ENGOT-cx11/GOG-3047/KEYNOTE-A18 study, we determined that pembrolizumab, when administered in combination with and after chemoradiotherapy, provides an overall survival benefit as compared with chemoradiotherapy alone for the treatment of newly diagnosed, high-risk, locally advanced cervical cancer. On the basis of these results, the trial met its second protocol-specified primary objective. Adverse events were consistent with the prior interim analysis and the known safety profiles of each regimen.

Implications of all the available evidence

To our knowledge, this is the first phase 3 study to report a statistically significant and clinically meaningful improvement in overall survival with the combination of a PD-1 inhibitor with modern, high-quality chemoradiotherapy in newly diagnosed, high-risk, locally advanced cervical cancer. These data support this strategy as a new standard of care for this population.

Source: The Lancet

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