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

I Vergote; E Van Nieuwenhuysen; A Casado; A Laenen; D Lorusso; E I Braicu; E Guerra-Alia; P Zola; P Wimberger; P R Debruyne; E Falcó; A Ferrero; M Z Muallem; J Kerger; E García-Martinez; S Pignata; J Sehouli; T Van Gorp; C Gennigens; M J Rubio

doi:10.1016/j.ygyno.2023.04.028

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

Gynecol Oncol. 2023 Jul:174:80-88. doi: 10.1016/j.ygyno.2023.04.028. Epub 2023 May 9.

Authors

I Vergote¹, E Van Nieuwenhuysen², A Casado³, A Laenen⁴, D Lorusso⁵, E I Braicu⁶, E Guerra-Alia⁷, P Zola⁸, P Wimberger⁹, P R Debruyne¹⁰, E Falcó¹¹, A Ferrero¹², M Z Muallem¹³, J Kerger¹⁴, E García-Martinez¹⁵, S Pignata¹⁶, J Sehouli¹³, T Van Gorp², C Gennigens¹⁷, M J Rubio¹⁸

Affiliations

¹ Belgium and Luxembourg Gynaecological Oncology Group (BGOG) and University Hospitals Leuven, Division of Gynaecological Oncology, Leuven, European Union, Belgium. Electronic address: Ignace.vergote@uzleuven.be.
² Belgium and Luxembourg Gynaecological Oncology Group (BGOG) and University Hospitals Leuven, Division of Gynaecological Oncology, Leuven, European Union, Belgium.
³ Hospital Clínico San Carlos, Spain and Grupo Español de Cáncer de Ovario (GEICO), Madrid, Spain.
⁴ Leuven Biostatistics and Statistical Bioinformatics Centre, KU Leuven, Leuven, Belgium.
⁵ Multicentre Italian Trials in Ovarian Cancer and Gynecologic malignancies (MITO) and Fondazione Policlinico Universitario Gemelli IRCCS and Catholic University of Sacred Heart, Roma, Italy.
⁶ Nord-Ostdeutsche Gesellschaft für Gynäkologische Onkologie e.V (NOGGO) and Department of Gynecology with Center for Oncological Surgery, Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Virchow Campus Clinic, Charité Medical University, Berlin, Germany; Stanford University, Department of Obstetrics and Gynecology, CA, USA.
⁷ Hospital Universitario Ramón y Cajal, and GEICO, Madrid, Spain.
⁸ Mario Negri Gynecologic Oncology Group (MaNGO) and Department of Surgical Sciences Università degli Studi di Torino, Italy.
⁹ NOGGO and Technische Universität Dresden and NCT Dresden, Dresden, Germany.
¹⁰ BGOG and Kortrijk Cancer Centre, AZ Groeninge, Kortrijk, Belgium; School of Life Sciences, Anglia Ruskin University, Cambridge, UK; School of Nursing & Midwifery, University of Plymouth, Plymouth, UK.
¹¹ GEICO and Policlinica Miramar, Palma de Mallorca, Spain.
¹² MaNGO and Mauriziano Hospital and University of Torino, Torino, Italy.
¹³ Nord-Ostdeutsche Gesellschaft für Gynäkologische Onkologie e.V (NOGGO) and Department of Gynecology with Center for Oncological Surgery, Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Virchow Campus Clinic, Charité Medical University, Berlin, Germany.
¹⁴ BGOG and Instituut Jules Bordet, Brussels, Belgium.
¹⁵ Hospital General Universitario Morales Meseguer, Murcia, Spain and GEICO.
¹⁶ MITO and Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale Napoli, Italy.
¹⁷ BGOG and CHU de Liège, Liège, Belgium.
¹⁸ Hospital Reina Sofía, Córdoba, Spain and GEICO.

PMID: 37167896
DOI: 10.1016/j.ygyno.2023.04.028

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: The study met its primary endpoint with a prolonged PFS in the N arm. No new safety signals were observed.

Keywords: Angiogenesis; Cervical cancer; Chemotherapy; Nintedanib; Recurrent.

Publication types

Randomized Controlled Trial
Clinical Trial, Phase II
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / adverse effects
Carboplatin
Double-Blind Method
Female
Humans
Lung Neoplasms* / drug therapy
Neoplasm Recurrence, Local / pathology
Paclitaxel
Uterine Cervical Neoplasms* / drug therapy
Uterine Cervical Neoplasms* / etiology
Vascular Endothelial Growth Factor A

Substances

Carboplatin
nintedanib
Vascular Endothelial Growth Factor A
Paclitaxel