VP4_2021 - EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9: Interim analysis of phase III trial of cemiplimab vs investigator’s choice (IC) chemotherapy (chemo) in recurrent/metastatic (R/M) cervical carcinoma

Abstract

K.S. Tewari¹, B.J. Monk², I. Vergote³, A. Miller⁴, A.C. de Melo⁵, H.S. Kim⁶, Y.M. Kim⁶, A. Lisyanskaya⁷, V. Samouëlian⁸, D. Lorusso⁹, F. Damian¹⁰, C-L. Chang¹¹, E.A. Gotovkin¹², S. Takahashi¹³, D. Ramone¹⁴, J. Pikiel¹⁵, J. Li¹⁶, M. Mathias¹⁶, M.G. Fury¹⁶, A. Oaknin^17
1Department of Obstetrics & Gynecology, University of California Irvine, Orange, CA, USA, ²Arizona Oncology (US Oncology Network) University of Arizona, Creighton University, Division of Gynecologic Oncology, Arizona, AZ, USA, ³Department of Obstetrics and Gynecology and Gynecologic Oncology, University Hospitals, Leuven, Belgium, ⁴Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA, ⁵Division of Clinical Research, Brazilian National Cancer Institute, Rio de Janeiro, Brazil, ⁶Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Republic of Korea, ⁷Department of Gynaecological Oncology, St. Petersburg State Budgetary Institution of Healthcare, St. Petersburg, Russian Federation, ⁸Gynecology Oncology, CHUM, CRCHUM, Université de Montréal, Montreal, QC, Canada, ⁹Gynaecology Oncology Unit, Fondazione Policlinico Universitario A Gemelli IRCCS and Catholic University of Sacred Heart, Rome, Italy, ¹⁰Gynaecology, Hospital Sao Lucas PUCRS, Porto Alegre, Brazil, ¹¹Gynaecology, MacKay Memorial Hospital, Taipei, Taiwan, ¹²Gynaecology, State Budget Healthcare Institution Ivanovo Regional Oncology Dispensary, Ivanovo, Russian Federation, ¹³Department of Medical Oncology, The Cancer Institute Hospital of JFCR, Tokyo, Japan, ¹⁴Clinical Research Department, Barretos Cancer Hospital (Pio XII Foundation), Barretos, Brazil, ¹⁵Gynaecology, Szpitale Pomorskie, Gdynia, Poland, ¹⁶Clinical Sciences Oncology, Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA, ¹⁷Gynaecologic Cancer Programme, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
Background: Salvage chemo is ineffective for patients (pts) with R/M cervical cancer following progression on first-line (1L) platinum-based chemo + bevacizumab.
Methods: EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 is an open-label, randomised (1:1), multi-centre, phase III trial of anti-programmed cell death (PD)-1 cemiplimab vs. IC single agent chemo in R/M cervical cancer that has progressed after 1L platinum-based treatment (tx). Pts were enrolled regardless of PD-L1 expression; received cemiplimab 350 mg IV every 3 wks or IC chemo (pemetrexed, vinorelbine, gemcitabine, irinotecan or topotecan), up to 96 wks; and were stratified by histology (squamous cell carcinoma [SCC] / adenocarcinoma or adenosquamous [AC]). Primary endpoint was overall survival (OS), analysed hierarchically in pts with SCC followed by total population (SCC + AC). Additional endpoints included progression-free survival (PFS), objective response rate (ORR), quality of life (QoL) and safety. Interim analysis was scheduled when 85% events occurred among SCC pts.
Results: 608 pts were randomised: median age, 51 years [range, 22‒87]; 477 SCC, 131 AC; ECOG performance score: 0 [46.5%], 1 [53.5%]. Median cemiplimab exposure was 15 wks (range, 1.4‒100.7). At interim analysis, OS (Table), PFS, ORR in overall and SCC populations, and mean change from baseline QoL in SCC, favoured cemiplimab. Most common tx emergent adverse events (AEs) of any grade for cemiplimab vs. IC chemo were anaemia (25% vs. 45%), nausea (18% vs. 33%) and vomiting (16% vs. 23%). Discontinuation due to AEs occurred in 8% (cemiplimab) and 5% (IC chemo).
Conclusions: Cemiplimab significantly improves OS over single agent chemo for pts with R/M cervical cancer after 1L platinum-based tx regardless of PD-L1 status or histology. No new safety signals were observed.
Cemiplimab median OS months (n)
IC chemo median OS months (n)
Hazard ratio for death (95% confidence interval)
P value

Total population
12.0 (n=304)
8.5 (n=304)
0.69 (0.56‒0.84)
P<0.001

SCC population
11.1 (n=239)
8.8 (n=238)
0.73 (0.58‒0.91)
P=0.003

AC population
13.3 (n=65)
7.0 (n=66)
0.56 (0.36‒0.85)
P<0.005
(nominal P value, not adjusted for multiplicity)


Clinical trial identification: NCT03257267.
Editorial acknowledgement: Writing support was provided by Randall Janairo, PhD, of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc. and Sanofi.
Legal entity responsible for the study: Regeneron Pharmaceuticals, Inc., Sanofi, and GOG and ENGOT.
Funding: Regeneron Pharmaceuticals, Inc. and Sanofi.
Disclosure:
K.S. Tewari: Financial Interests, Personal, Other, Honoraria: Tesaro, Clovis Oncology; Financial Interests, Personal, Advisory Role, Consulting or advisory roles: Genentech, Tesaro, Clovis, AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Genentech, AstraZeneca, Merck, Tesaro, Clovis; Financial Interests, Institutional, Research Grant: AbbVie, Genentech, Morphotek, Merck, Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Other, Travel, accommodations, expenses: Genentech.
B.J. Monk: Financial Interests, Personal, Other, Consulting honoraria: Aravive, Asymmetric Therapeutics, Boston Biomedical, ChemoCare, ChemoID, Circulogene, Conjupro Biotherapeutics, Eisai, Geistlich, Genmab/Seattle Genetics, Gynecologic Oncology Group Foundation, ImmunoGen, Immunomedics, Incyte, Laekna Health Care; Financial Interests, Personal, Other, Consulting honoraria: Mateon/Oxigene, Merck, Mersana, Myriad, Nucana, Oncomed, Oncoquest, Oncosec, Perthera, Pfizer, Precision Oncology, Puma, Regeneron, Samumed, Takeda, VBL, Vigeo; Financial Interests, Personal, Speaker’s Bureau, Consulting/speaker honoraria: AstraZeneca, Clovis, Janssen/Johnson & Johnson, Roche/Genentech, Tesaro/GSK.
I. Vergote: Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Elevar Therapeutics, Genmab, GlaxoSmithKline, Immunogen, Merck Sharp & Dohme, Oncoinvent; Financial Interests, Personal, Research Grant: Genmab, F. Hoffmann-La Roche.
A.C. de Melo: Financial Interests, Personal, Advisory Board: MSD, BMS, Libbs; Financial Interests, Personal, Other, Support for travel or accommodation: AstraZeneca, MSD, BMS,d Roche; Financial Interests, Institutional, Research Grant: Clovis Oncology, BMS, Roche, Novartis, Amgen, MSD, Lilly, Pierre Fabre, Sanofi, Pfizer.
Y.M. Kim: Financial Interests, Personal, Stocks/Shares: Johnson & Johnson, Genolution; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Research Grant: Regeneron Pharmaceuticals, Inc., Roche.
D. Lorusso: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Clovis Oncology, Genmab, Immunogen, Merck Serono, MSD, PharmaMar, Roche, GSK; Financial Interests, Institutional, Research Grant: Clovis Oncology, MSD, PharmaMar, Roche, GSK; Financial Interests, Personal, Expert Testimony: Clovis Oncology; Financial Interests, Personal, Principal Investigator: AstraZeneca, Clovis Oncology, Genmab, Immunogen, MSD, PharmaMar, Roche, GSK; Financial Interests, Personal, Other, Travel support: AstraZeneca, PharmaMar, Roche, GSK; Non-Financial Interests, Personal, Other, Nonfinancial member interests: European Network for Gynaecological Oncological Trial groups (ENGOT), European Society of Gynaecological Oncology (ESGO), European Society for Medical Oncology (ESMO), Gynecologic Cancer Intergroup (GCIG; Board of Directors); Non-Financial Interests, Personal, Other, Nonfinancial member interests: Italian Association of Medical Oncology (AIOM), Multicenter Italian Trials in Ovarian Cancer (MITO).
S. Takahashi: Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo, Eisai, Bayer, Taiho Pharmaceutical, MSD, Novartis, Chugai Pharma, AstraZeneca, Bristol-Myers Squibb Japan, Ono Pharmaceutical, Nihonkayaku, Pfizer, Lilly Japan; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Research Grant: Daiichi Sankyo, Sanofi, Eisai, Bayer, Taiho Pharmaceutical, MSD, Novartis, Chugai Pharma, AstraZeneca, Bristol-Myers Squibb, Lilly, Ono Pharmaceutical, PharmaMar, Pfizer/EMD Serono; Financial Interests, Personal, Other, Travel, accommodation, and expenses: Daiichi Sankyo, Novartis.
J. Li: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.
M. Mathias: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.
M.G. Fury: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.
A. Oaknin: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, PharmaMar, Clovis Oncology, Tesaro, Inmunogen, Genmab, Mersana Therapeutic, GSK, Deciphera Pharmaceuticals; Financial Interests, Personal, Other, Support for travel or accommodation: Roche, AstraZeneca, PharmaMar.
All other authors have declared no conflicts of interest.