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Clinical Trial
. 2025 Aug:199:88-95.
doi: 10.1016/j.ygyno.2025.06.003. Epub 2025 Jun 30.

Patient-reported outcomes from the phase 3, randomized, double-blind, placebo-controlled ENGOT-cx11/GOG-3047/KEYNOTE-A18 study of pembrolizumab plus concurrent chemoradiotherapy in participants with high-risk locally advanced cervical cancer

Leslie Randall  1 , Yang Xiang  2 , Takashi Matsumoto  3 , Diana Giannarelli  4 , Dency Pilar Milla  5 , Karla Alejandra Lopez  6 , Alejandro Acevedo  7 , Julia Vizkeleti  8 , Ritu Salani  9 , Angelica Nogueira-Rodrigues  10 , Fernando Contreras Mejia  11 , Jacob Korach  12 , Hüseyin Akilli  13 , Jung-Yun Lee  14 , Valeriya Vladimirovna Saevets  15 , Vanessa Samouelian  16 , Jalid Sehouli  17 , Ekkasit Tharavichikul  18 , Vladyslav Sukhin  19 , Nicoletta Colombo  20 , Chih-Long Chang  21 , Juan F Cueva  22 , Susan Lalondrelle  23 , Edgar Petru  24 , Elizabeth Szamreta  25 , Allison Martin Nguyen  26 , Karin Yamada  27 , Kan Li  28 , Sandro Pignata  29 , Domenica Lorusso  30
Affiliations
Free article
Clinical Trial

Patient-reported outcomes from the phase 3, randomized, double-blind, placebo-controlled ENGOT-cx11/GOG-3047/KEYNOTE-A18 study of pembrolizumab plus concurrent chemoradiotherapy in participants with high-risk locally advanced cervical cancer

Leslie Randall et al. Gynecol Oncol. 2025 Aug.
Free article

Abstract

Objective: In ENGOT-cx11/GOG-3047/KEYNOTE-A18 (NCT04221945), pembrolizumab (vs placebo) + concurrent chemoradiotherapy (CCRT) followed by pembrolizumab (vs placebo) significantly improved progression-free survival and overall survival in participants with newly diagnosed, high-risk locally advanced cervical cancer (LACC). We report patient-reported outcomes (PROs) from the study.

Methods: Participants (≥18 years) with high-risk LACC (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA) were randomized 1:1 to 5 cycles of pembrolizumab 200 mg or placebo Q3W plus CCRT, followed by 15 cycles of pembrolizumab 400 mg or placebo Q6W. CCRT was 5 cycles (optional 6th dose) of cisplatin 40 mg/m2 Q1W plus external beam radiotherapy followed by brachytherapy. Secondary PRO endpoints included EORTC QLQ-C30 GHS/QoL and physical functioning subscales and EORTC QLQ-CX24 symptom experience scale; EQ-5D-5L visual analogue scale (VAS) was an exploratory endpoint. No alpha was assigned to the PRO analyses.

Results: 1008 (95.1 %) of 1060 randomized participants were included in the PRO full analysis set population. No meaningful between-group differences were observed for any of the prespecified PRO instruments. Between-group differences (95 % CIs) in least-squares mean score changes from baseline to week 36 (primary time point) were 0.57 (-2.34 to 3.49) for QLQ-C30 GHS/QoL, 0.64 (-1.54 to 2.82) for QLQ-C30 physical functioning, 0.54 (-1.02 to 2.09) for QLQ-CX24 symptom experience, and -0.55 (-2.97 to 1.86) for EQ-5D-5L VAS. Empirical mean score changes over time and the proportions of participants whose scores improved, remained stable, or deteriorated over time were similar between treatment arms.

Conclusions: Pembrolizumab+CCRT did not negatively impact participants' health-related quality of life.

Keywords: Chemotherapy; Health-related quality of life; Locally advanced cervical cancer; Patient-reported outcomes; pembrolizumab.

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Conflict of interest statement

Declaration of competing interest Leslie Randall: Research grants to institution from MSD, Zentalis, Karyopharm, GOG Foundation, Regeneron, ImmunoGen, Inc., Acrivon, CanariaBio Inc., Corcept Therapeutics, and Seagen; Consulting fees from AstraZeneca, MSD, GSK, Genmab, Seagen, GOG Foundation, Zentalis, ImmunoGen, Stemline, Eisai, Caris, Nykode, Clovis, and Natera; Honoraria from Seagen and Genmab; Leadership or fiduciary role for GOG Foundation. Yang Xiang: Research funding from MSD. Takashi Matsumoto: Honoraria from Chugai Pharma, AstraZeneca, MSD, Takeda, Tsumura & Co., Taiho Pharmaceutical, NanoCarrier, Aska Pharma, Lumenis, Zeria Pharmaceutical, Eisai, Sanofi, Hologic, and Novelpharm. Diana Giannarelli: Consulting/Advisory role for Sanofi and Amgen. Dency Pilar Milla: None declared. Karla Alejandra Lopez: None declared. Alejandro Acevedo: Honoraria from MSD, Roche, BMS, Pfizer, Gilead, Sanofi, Amgen, and AstraZeneca. Julia Vizkeleti: Employment at the National Institute of Oncology, Budapest, Hungary. Ritu Salani: Honoraria from MSD, Pfizer, Regeneron, AbbVie/Immunogen, Eisai, GSK, Genmab, and Genentech; travel support from GSK, MSD, and Genmab; royalties or licenses from Up to Date and Elsevier. Angelica Nogueira-Rodrigues: Personal honoraria for advisory boards from AbbVie, AstraZeneca, Daiichi Sankyo, Eisai, Gilead, GSK, Immunogen, MSD, Novartis, Pfizer, and Roche; President elect for the Brazilian Society of Medical Oncology (not recompensed); Chair LACOG (not recompensed); Director of strategic planning Brazilian Group of Gynecologic Cancer (not recompensed). Fernando Contreras Mejia: Honoraria from AstraZeneca, GSK, MSD, Roche, Eli-Lilly, Novartis, and BMS; consultant/advisor for GSK, Janssen, Pfizer, and MSD. Jacob Korach: None declared. Hüseyin Akilli: None declared. Jung-Yun Lee: Research grants from Advenchen, Ascendis Pharma, Alkermes, AstraZeneca, Beigene, BergenBio, BioNTech, BMS, CanariaBio, Corcept, Cellid, CKD, Clovis Oncology, Eisai, Genmab, Genemedicine, GII, GSK, ImmunoGen, Janssen, Kelun, Merck & Co., Inc., Mersana, MSD, Novartis, Onconic Therapeutics, ONO, Regeneron, Roche, Seagen, Sutro, Synthon, and Takeda; consulting fees from AstraZeneca, CanariaBio, Genmab, GII, ImmunoGen, MSD, Seagen, Merck & Co., Inc., Sutro, and Regeneron; honoraria for lectures and presentations from AstraZeneca, Eisai, MSD, Roche, and Takeda. Valeriya Vladimirovna Saevets: Honoraria and consultant/advisory fees from AstraZeneca, MSD, and BIOCAD. Vanessa Samouelian: Honoraria from AstraZeneca, GlaxoSmithKline, Eisai, and MSD; consultant/advisor for AstraZeneca, GlaxoSmithKline, Eisai, and MSD. Jalid Sehouli: Research funding from Roche, AstraZeneca, Bayer, Clovis Oncology, GSK, Lilly, Tesaro, IQVIA, Mural, and MSD; honoraria from Tesaro, GSK, PharmaMar, AstraZeneca, Clovis Oncology, Bayer, Roche, Vifor, Hexal AG, Novartis, Eisai, Esteve Pharmaceuticals, Incyte Biosciences, Phytolife Nutrition, JenaPharm, Kyowa Kirin, Oncoinvent AS, Daiichi, Medtronic Covidien, and Amgen; consultant for Tesaro, Merck & Co., Inc., Pfizer, PharmaMar, Clovis Oncology, AstraZeneca, Roche, GSK, MSD, Eisai, Novocure, Oncoinvent, Intuitive Surgical, Seagan, Bayer Vital, Mundipharma, Sanofi-Aventis Deutschland GmbH, Immunogen, Tubulis GmbH, Daiichi Sankyo, Bristol Myers, and Karyopharm Therapeutics. Ekkasit Tharavichikul: Honoraria from Elekta; travel support to ESTRO meets Asia 2024 in Kuala Lumpur, Malaysia. Vladyslav Sukhin: None declared. Nicoletta Colombo: Employment at Sarepta Therapeutics; honoraria from Roche/Genentech, AstraZeneca, GlaxoSmithKline, MSD Oncology, Clovis Oncology, Pfizer, Amgen, Immunogen, Novartis, Pfizer, mersana, Eisai, Advaxis, and Nuvation Bio; consulting/advisor for Roche/Genentech, AstraZeneca, Clovis Oncology, Pfizer, MSD Oncology, GlaxoSmithKline, Immunogen, Pfizer, mersana, Eisai, Advaxis, and Nuvation Bio. Chih-Long Chang: Honoraria from AstraZeneca, MSD, and TTY Biopharm. Juan F. Cueva: Honoraria and consultant/advisor from AstraZeneca, Clovis, GSK, MSD, Roche, and PharmaMar; travel/accommodations from MSD, AstraZeneca, Clovis, PharmaMar, Roche, and GSK. Susan Lalondrelle: Honoraria from GSK, MSD, and Elekta; consulting for GSK and MSD. Edgar Petru: Honoraria for lectures and advisory boards from Roche, MSD, and GSK; research support to institution from MSD. Elizabeth Szamreta, Allison Martin Nguyen, Karin Yamada, and Kan Li: Employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, who may own stock and/or hold stock options in Merck & Co., Inc., Rahway, NJ, USA. Sandro Pignata: Research funding from AstraZeneca, GSK, MSD, Roche, and Pfizer; honoraria from Novartis, AstraZeneca, MSD, Pharmamar, and GSK. Domenica Lorusso: Invited speaker for AstraZeneca, Clovis Oncology, Daiichi Sankyo, Genmab, GSK, Immunogen, MSD, Novocure, and Seagen; consultant for MSD and Novartis; advisory board position for AstraZeneca, Clovis Oncology, Corcept, Daiichi Sankyo, Genmab, GSK, Immunogen, MSD, Oncoinvest, Novocure, Seagen, and Sutro; research funding to institution from AstraZeneca, Clovis Oncology, Pharmaand, Genmab, GSK, Immunogen, Incyte, MSD, Novartis, PharmaMar, Roche, Seagen, Alkermes, and Corcept; Principal Investigator of clinical trials (no compensation received) for AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, Incyte, MSD, Novartis, PharmaMar, Roche, Seagen, and Corcept; Board of Directors for GCIG; President Elect for MITO, Coordinating Member for ENGOT; travel support from AstraZeneca, Menarini, GSK, and MSD.

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