Randomized phase II BGOG/ENGOT-cx1 study of paclitaxel-carboplatin with or without nintedanib in first-line recurrent or advanced cervical cancer.

Nintedanib is an oral tyrosine kinase inhibitor targeting, among others, vascular endothelial growth factor receptor. The aim was to establish the role of nintedanib in addition to paclitaxel and carboplatin in first-line recurrent/metastatic cervical cancer. Double-blind phase II randomized study in patients with first-line recurrent or primary advanced (FIGO stage IVB) cervical cancer. Patients received carboplatin-paclitaxel with oral nintedanib 200 mg BID/placebo. The primary endpoint was progression-free survival (PFS) at 1.5 years and α = 0.15, β = 80%, one sided. 120 patients (62 N, 58C) were randomized. Median follow-up was 35 months. Baseline characteristics were similar in both groups (total population: squamous cell carcinoma 62%, prior radiotherapy 64%, primary advanced 25%, recurrent 75%). The primary endpoint was met with a PFS at 1.5 years of 15.1% versus 12.8% in favor of the nintedanib arm (p = 0.057). Median overall survival (OS) was 21.7 and 16.4 months for N and C, respectively. Confirmed RECIST response rate was 48% for N and 39% for C. No new adverse events were noted for N. However, N was associated with numerically more serious adverse events for anemia and febrile neutropenia. Global health status during and at the end of the study was similar in both arms. The study met its primary endpoint with a prolonged PFS in the N arm. No new safety signals were observed.

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Déclaration de conflit d'intérêts

Declaration of Competing Interest Vergote I. as corresponding author declares consulting fees from Agenus, Akesobio, AstraZeneca, Bristol Myers Squibb, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, Exelixis, F. Hoffmann-La Roche, Genmab, GSK, Immunogen, Jazzpharma, Karyopharm, Mersana, MSD, Novocure, Novartis, Oncoinvent, OncXerna, Regeneron, Sanofi, Seagen, Sotio, Verastem Oncology, Zentalis; Contracted research (via KULeuven) from Oncoinvent AS; Corporate sponsored research from Amgen and Roche and accommodations and travel expenses from Karyopharm, Genmab and Novocure. Van Nieuwenhuysen E. declares consulting/advisory board fees from AstraZeneca, Regeneron; research support from Eli Lilly and travel expenses from Roche and PharmaMar. Casado A. declares consulting or advisory role from Roche Spain, PharmaMar, Eisai, Merck Sharp & Dohme, Eisai (all personal); research funding from PharmaMar (institutional); travel and accommodation support from PharmaMar, Roche, Lilly Spain (all personal); other relationship with Lilly (institutional). Laenen A. declares no conflicts. Lorusso D. declares consultant honoraria from AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Seagen, Novartis and PharmaMar; invited member of advisory board from Oncoinvest, Corcept, Sutro; invited speaker and member of advisory boards from AstraZeneca, Immunogen, GSK, Seagen, Genmab; research institutional funding from Clovis Oncology, GSK, MSD and PharmaMar; grants for traveling: AstraZeneca, Clovis Oncology, GSK. Braicu E.I. received research funding from Bayer, Roche Diagnostics, Tesaro, GSK, and AstraZeneca and received personal fees from AstraZeneca, Clovis, GSK, Tesaro, EISAI, RochePharma, and Roche Diagnostics. Guerra-Alia E. has received advisory/consultancy honorarium from AstraZeneca-MSD, Clovis Oncology, GSK-Tesaro, PharmaMar, Roche; she has received speaker bureau/expert testimony honorarium from AstraZeneca-MSD, PharmaMar, Roche, GSK-Tesaro, Clovis and she received travel/accommodation/expenses from Roche, GSK-Tesaro and Baxter. Zola P. declares consulting fees from Astrazeneca. Wimberger P. has received research funding from Amgen, AstraZeneca, MSD, GlaxoSmithKline, Novartis, Pfizer, Roche Pharma, Clovis, Lilly, honoraria from Amgen, AstraZeneca, MSD, GlaxoSmithKline, Novartis, Pfizer, Roche Pharma, Clovis, TEVA, Eisai, Lilly, Gilead, Daichii Sankyo. He participates at advisory boards from Amgen, AstraZeneca, MSD, GlaxoSmithKline, Novartis, Pfizer, Roche Pharma, Clovis, TEVA, Eisai, Lilly, Gilead and Daichii Sankyo. Debruyne P.R. received grants from Pfizer (institutional); consulting fees for Advisory Boards from BMS, Merck Pfizer, Ipsen; honoraria for lectures from Bayer; travel support from Janssen; (Substitute) Board Member, Clinical Trials College, Federal Public Service, Kingdom of Belgium; stock or stock options from Alkermes and Biocartis Group NV. Ferrero A declares honoraria from GlaxoSmithKline, Clovis, Astra Zeneca-MSD; invited member of advisory boards from Astra Zeneca-MSD. Muallem MZ received consulting fees from Styker, Intuitive and BD. Garcia-Martinez E. received accommodations and travel expenses from GSK, Roche, MSD and consulting or educational fees from GSK, AstraZeneca, Pharmamar, MSD. Pignata S. has no COI related to this paper. Sehouli J. received consulting fees from Tesaro, Merck/Pfizer, PharmaMar, Clovis Oncology, Eisai, Oncoinvent, AstraZeneca, Roche Pharma, GlaxoSmith, MSD, Novocure; honoraria for lectures from Tesaro, PharmaMar, Clovis, Roche, Vifor Pharma, Novartis Pharma, GlaxoSmith, AstraZeneca, Bayer, PharmaMar, Hexal AG; patents from Roche Pharma, Bayer, GlaxoSmith, Tesaro, AstraZeneca, Clovis and Lilly. Van Gorp T. received grants from Amgen, Roche and AstraZeneca (institutional); consulting fees from AstraZeneca, Eisai Europe, OncXerna Therapeutics, MSD/Merck, GSK, ImmunoGen and Seagen (all institutional); he received travel support from Amgen, Pfizer, Roche, Sanofi-Aventis, Novartis, Roche, Immunogen, MSD, AstraZeneca, PharmaMar and GSK. Gennigens Ch. declares no disclosures for the present manuscript; grants/contracts from AstraZeneca, consulting fees from Ipsen, GSK and MSD; honoraria for lectures etc. from MSD, BMS, Ipsen, Pfizer, Pharmamar, AstraZeneca, GSK; support for meetings and/or travel: Ipsen, Pharmamar, Pfizer, MSD, GSK; participation on data safety monitoring board or Advisory Board: MSD, BMS, Ipsen, AstraZeneca, GSK, Eisai. Rubio MJ. has served on advisory boards for MSD, AstraZeneca, Roche, GSK, Clovis, PharmaMar and received support for travel or accommodation from Roche, AstraZeneca, PharmaMar, MSD and GSK.