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Clinical Trial
. 2025 Aug:199:79-87.
doi: 10.1016/j.ygyno.2025.06.008. Epub 2025 Jun 30.

NSGO-FANDANGO/ENGOT-EN1: A randomized phase II study of first-line combination chemotherapy with nintedanib/placebo in advanced/recurrent endometrial cancer

Kristina Lindemann  1 , Dominique Berton  2 , Jalid Sehouli  3 , René DePont Christensen  4 , Sevilay Altintas  5 , Anja Ør Knudsen  6 , Pierre-Etienne Heudel  7 , Beyhan Ataseven  8 , Ignace Vergote  9 , Gabriel Lindahl  10 , Coriolan Lebreton  11 , Fabienne Schochter  12 , Annika Auranen  13 , Philippe Follana  14 , Kristine Madsen  4 , Frédéric Selle  15 , Karen Stampe Petersson  4 , Florence Joly  16 , Elena Ioana Braicu  3 , Mansoor Raza Mirza  17
Affiliations
Clinical Trial

NSGO-FANDANGO/ENGOT-EN1: A randomized phase II study of first-line combination chemotherapy with nintedanib/placebo in advanced/recurrent endometrial cancer

Kristina Lindemann et al. Gynecol Oncol. 2025 Aug.

Abstract

Objective: Patients with advanced or recurrent endometrial cancer (EC) have poor prognosis despite treatment with combination chemotherapy. This study explored the preliminary efficacy of the potent oral tyrosine kinase inhibitor nintedanib (N), in addition to chemotherapy.

Methods: Patients with histologically confirmed stage FIGO 2009 stage IIIC2-IV or recurrent EC were randomized 1:1 to receive N 200 mg or placebo (P), twice daily days 2-21 during chemotherapy (six cycles of Carboplatin (AUC5) and paclitaxel (175 mg/m2) every 21 days (TC)) and in maintenance until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was progression-free survival (PFS).

Results: Between November 30th, 2016, and January 11th, 2019 146 participants (mean age 66.1 years) were randomized and had received at least one dose of N/P: 72 patients to the N + TC arm and 74 to the P + TC arm. After median follow-up time of 43.9 months (95 % CI: 41.8-45.6), median PFS was 8.2 63 months (95 % CI: 5.77-10.27) in the N + TC arm and 7.1 months (95 % CI: 5.40-9.10) in the P + TC arm (HR 0.99, 95 % CI: 0.69-1.43, p = 0.992). There was no difference in median overall survival (OS) (HR 0.82; 96 % CI: 0.54-1.25, p = 0.365). Treatment-emergent grade 3-4 adverse events were higher in N + TC vs P + TC arm, in particular increase in blood alanine aminotransferase (18.1 % vs 4.1 %) and diarrhea (10.8 % and 1.3 %).

Conclusions: Addition of nintedanib to chemotherapy did not improve PFS nor OS. Phase III evaluation of this regimen is not recommended.

Keywords: Angiokinase inhibitor; Chemotherapy; Endometrial cancer; Nintedanib; Phase 3 placebo-controlled trial; VEGF receptor.

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Conflict of interest statement

Declaration of competing interest KL reports research funding (to institution) from GSK; honoraria from Eisai and MSD; and board roles for Eisai, MSD, Nykode Therapeutics, AstraZeneca, GSK, and Karyopharm Therapeutics. DB reports no disclosures of potential conflicts of interest. JS reports research funding from Roche Pharmaceuticals, AstraZeneca, Bayer, Clovis Oncology, GSK, Lilly, Tesaro, IQVIA, Mural Oncology, MSD; honoraria from Tesaro, GSK, PharmaMar, AstraZeneca, Clovis Oncology, Bayer, Roche Pharmaceuticals, Vifor Pharma, Hexal AG, Novartis, Eisai, Esteve Pharmaceuticals, Incyte Biosciences, PhytoLife Nutrition, Jenapharm, Kyowa Kirin, Oncoinvent, Daiichi Sankyo, Medtronic Covidien, Amgen; consulting/advisory roles for Tesaro, Merck, Pfizer, PharmaMar, Clovis Oncology, AstraZeneca, Roche Pharmaceuticals, GSK, MSD, Eisai, Novocure, Oncoinvent, Intuitive Surgical, Seagen, Bayer Vital, Mundipharma, Sanofi, ImmunoGen, Tubulis, Daiichi Sankyo, Bristol Myers Squibb, Karyopharm Therapeutics. RdPC reports no disclosures of potential conflicts of interest. SA reports no disclosures of potential conflicts of interest. AØK reports no disclosures of potential conflicts of interest. PEH reports research grants and personal fees and non-financial support from Pfizer, Lilly, Daiichi Sankyo, and AstraZeneca; research grants and non-financial support from Novartis and Roche; and personal fees and non-financial support from Seagen, Gilead Sciences, and MSD. BA reports lectures and board roles and travel/accommodation/expenses from Roche, GSK, Celgene Corporation, Clovis Oncology, AstraZeneca, Novartis, MSD, Eisai, Lilly, Medkoncept, Medupdate, Eickeler, StreamedUp, ClinSol, Esteve Pharmaceuticals, Pfizer, Daiichi Sankyo, and Sanofi. IV reports consulting/advisory roles for Akeso Biopharma, Bristol Myers Squibb, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, Roche, Genmab, GSK, ITM Radioparma, Jazz Pharmaceuticals, Karyopharm Therapeutics, MSD, Novocure, Oncoinvent, Sanofi, Regeneron Pharmaceuticals, Seagen, Sotio, and Zentalis Pharmaceuticals; consulting/committee roles for Agenus, AstraZeneca, Corcept Therapeutics, Daiichi Sankyo, Exelixis, Genmab, Roche, ImmunoGen, Kronos Bio, Mersana Therapeutics, Novartis, OncXerna Therapeutics, Verastem Oncology. GL reports no disclosures of potential conflicts of interest. CL reports consulting/advisory roles for Eisai, GSK, Abbvie and AstraZeneca; honoraria from GSK, Eisai, MSD, Clovis Oncology, and AstraZeneca; and travel/accommodation/expenses from MSD and GSK. FS reports no disclosures of potential conflicts of interest. AA reports no disclosures of potential conflicts of interest. PF reports no disclosures of potential conflicts of interest. KM reports honoraria from GSK and AstraZeneca; travel/accommodation/expenses from GSK and AstraZeneca; consulting/committee role for Kancera AB; and other relationship with NSGO-CTU. FS reports honoraria from Roche, AstraZeneca, GSK and MSD; consulting roles for Roche, Clovis Oncology, GSK, AstraZeneca, MSD and Eisai; travel/accommodation/expenses from MSD, AstraZeneca and AbbVie; research funding (to institution) from AstraZeneca, Roche, and Karyopharm Therapeutics. KSP reports no disclosures of potential conflicts of interest. FJ reports lectures and scientific board roles for GSK, AstraZeneca, pharma&, MSD, and Eisai. EIB reports research funding (to institution) from AstraZeneca, MSD, Eisai, GSK, Immunogen, Bayer, Roche, and Roche Diagnostics; honoraria from AstraZeneca, GSK, ImmunoGen, TORLBio, MSD, Myriad; travel/accommodation/expenses from AstraZeneca; other relationship with NOGGO. MRM reports research funding from AstraZeneca, Boehringer Ingelheim, Pfizer, Tesaro, Clovis Oncology, Ultimovacs, Apexigen, and GSK; consulting fees from Karyopharm Therapeutics; honoraria from AstraZeneca, Eisai, GSK, MSD, Takeda Pharma, Tesaro, and Zai Lab; travel/accommodation/expenses from AstraZeneca, GSK, and Zai Lab; board roles for Allarity Therapeutics, AstraZeneca, BIOCAD, BioNTech, Boehringer Ingelheim, Clovis Oncology, Daiichi Sankyo, Duality Biologics, Eisai, Genmab, GSK, ImmunoGen, Incyte, Karyopharm Therapeutics, MSD, Mersana Therapeutics, Novartis, Nykode Therapeutics, Regeneron Pharmaceuticals, Roche, Seagen, Takeda Pharma, Tesaro, Zai Lab; leadership role and stock options for Karyopharm Therapeutics.

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