1. Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 trial
- Author
-
Lorusso, D, Xiang, Y, Hasegawa, K, Scambia, G, Leiva, M, Ramos-Elias, P, Acevedo, A, Cvek, J, Randall, L, Pereira de Santana Gomes, A, Contreras Mejia, F, Helpman, L, Akilli, H, Lee, J, Saevets, V, Zagouri, F, Gilbert, L, Sehouli, J, Tharavichitkul, E, Lindemann, K, Colombo, N, Chang, C, Bednarikova, M, Zhu, H, Oaknin, A, Christiaens, M, Petru, E, Usami, T, Liu, P, Yamada, K, Toker, S, Keefe, S, Pignata, S, Duska, L, Lorusso D., Xiang Y., Hasegawa K., Scambia G., Leiva M., Ramos-Elias P., Acevedo A., Cvek J., Randall L., Pereira de Santana Gomes A. J., Contreras Mejia F., Helpman L., Akilli H., Lee J. -Y., Saevets V., Zagouri F., Gilbert L., Sehouli J., Tharavichitkul E., Lindemann K., Colombo N., Chang C. -L., Bednarikova M., Zhu H., Oaknin A., Christiaens M., Petru E., Usami T., Liu P., Yamada K., Toker S., Keefe S. M., Pignata S., Duska L. R., Lorusso, D, Xiang, Y, Hasegawa, K, Scambia, G, Leiva, M, Ramos-Elias, P, Acevedo, A, Cvek, J, Randall, L, Pereira de Santana Gomes, A, Contreras Mejia, F, Helpman, L, Akilli, H, Lee, J, Saevets, V, Zagouri, F, Gilbert, L, Sehouli, J, Tharavichitkul, E, Lindemann, K, Colombo, N, Chang, C, Bednarikova, M, Zhu, H, Oaknin, A, Christiaens, M, Petru, E, Usami, T, Liu, P, Yamada, K, Toker, S, Keefe, S, Pignata, S, Duska, L, Lorusso D., Xiang Y., Hasegawa K., Scambia G., Leiva M., Ramos-Elias P., Acevedo A., Cvek J., Randall L., Pereira de Santana Gomes A. J., Contreras Mejia F., Helpman L., Akilli H., Lee J. -Y., Saevets V., Zagouri F., Gilbert L., Sehouli J., Tharavichitkul E., Lindemann K., Colombo N., Chang C. -L., Bednarikova M., Zhu H., Oaknin A., Christiaens M., Petru E., Usami T., Liu P., Yamada K., Toker S., Keefe S. M., Pignata S., and Duska L. R.
- Abstract
Background: At the first interim analysis of the phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study, the addition of pembrolizumab to chemoradiotherapy provided a statistically significant and clinically meaningful improvement in progression-free survival in patients with locally advanced cervical cancer. We report the overall survival results from the second interim analysis of this study. Methods: Eligible patients with newly diagnosed, high-risk (FIGO 2014 stage IB2–IIB with node-positive disease or stage III–IVA regardless of nodal status), locally advanced, histologically confirmed, squamous cell carcinoma, adenocarcinoma, or adenosquamous cervical cancer were randomly assigned 1:1 to receive five cycles of pembrolizumab (200 mg) or placebo every 3 weeks with concurrent chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Pembrolizumab or placebo and cisplatin were administered intravenously. Patients were stratified at randomisation by planned external beam radiotherapy type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), cervical cancer stage at screening (FIGO 2014 stage IB2–IIB node positive vs III–IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy [equivalent dose of 2 Gy]). Primary endpoints were progression-free survival per RECIST 1.1 by investigator or by histopathological confirmation of suspected disease progression and overall survival defined as the time from randomisation to death due to any cause. Safety was a secondary endpoint. Findings: Between June 9, 2020, and Dec 15, 2022, 1060 patients at 176 sites in 30 countries across Asia, Australia, Europe, North America, and South America were randomly assigned to treatment, with 529 patients in the pembrolizumab–chemoradiotherapy group and 531 patients in the placebo–chemoradiotherapy group. At the protocol-specified second interim analysis (dat
- Published
- 2024