Nintedanib(N) as switch maintenance treatment in malignant pleural mesothelioma (MPM) (NEMO): A double-blind randomized phase II trial (EORTC-08112-LCG)

BackgroundVEGF and FGFR play major roles in MPM tumorigenesis. Bevacizumab(bev)-platinum-pemetrexed (PP) with bev maintenance improved progression-free (PFS) and overall survival (OS) in the MAPS trial. N is an angiokinase inhibitor with antifibrotic properties targeting VEGF1-3, PDGFRA/B, FGFR1-3, SRC, ABL. VEGF inhibitors previously showed encouraging activity and N’s role as switch maintenance remained unknown. During enrolment, the LUME-Meso phase III trial reported no OS improvement for N-PP and N maintenance in epithelioid MPM and cediranib-PP demonstrated no significant PFS benefit (SWOG S0905).MethodsWe enrolled treatment naïve unresectable MPM (all histology), adequate organ function, no unstable co-morbidities, no N contraindication, performance status 0-2 and no progression after 4-6 cycles PP. Patients(pts) were randomized to N 200mg BID or placebo, continued until loss of clinical benefit, toxicity, or death. Primary endpoint was PFS, secondary endpoints were OS, time to treatment failure (TTF), overall response rate (ORR) and safety. 114 pts were planned for recruitment to target PFS HR=0.62.ResultsThe study closed due to poor accrual with 37 pts randomized. We present final analyses. Demographics/efficacy shown (Table). Grade≥3 adverse events (AEs) were observed in 27.8%(N) vs 10.5%(placebo), no deaths from toxicity. Commonest AEs were typical for N. Table: 1914P N, n=18 Placebo, n=19 HR (95% CI) Median follow up (mo) 48.7 42.4 M:F (n) 12:6 15:4 Epithelioid (%) 78 79 Median treatment duration (weeks) 11.8 24.3 PFS (mo) 3.4 4.6 2.25 (1.07-4.73) OS (mo) 13.1 38.9 2.38 (1.05-5.43) TTF (mo) 2.0 4.6 2.55 (1.22-5.32) Further anticancer treatment (%) 72 79 Further immunotherapy (%) 46 87 .ConclusionsDespite closing early, whilst imbalanced by subsequent immunotherapy use, NEMO suggests a detrimental effect of maintenance N compared with placebo (Sponsor, EORTC; Funding, Boehringer Ingelheim/EORTC; NCT02863055).Clinical trial identificationEORTC-08112-LCG; NCT02863055.Legal entity responsible for the studyEORTC.FundingBoehringer Ingelheim.DisclosureS. Popat: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Novartis, Amgen, Janssen, Daiichi Sankyo, AstraZeneca, Bayer, BMS, Blueprint, Merck Serono, Guardant Health, Takeda, Lilly, Roche, Turning Point Therapeutics, GSK, MSD, Pfizer, Sanofi, EQRx, AnHeart, Arcus Biosciences, Ellipses, Gilead, IO Biotech, Mirati; Financial Interests, Personal, Invited Speaker: Medscape, VJ Oncology, Novocure, PharmaMar; Financial Interests, Institutional, Other, Sub-investigator: Amgen; Financial Interests, Institutional, Coordinating PI: Ariad, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Takeda, Turning Point Therapeutics, Roche, Janssen, BMS, Lilly; Financial Interests, Institutional, Local PI: AstraZeneca, Roche, GSK, Trizel; Financial Interests, Institutional, Other, Sub-Investigator: MSD, Blueprint; Financial Interests, Institutional, Research Grant: Guardant Health; Non-Financial Interests, Leadership Role, Chair of Steering Committee, Unpaid: British Thoracic Oncology Group; Non-Financial Interests, Officer, Thoracic Faculty, Unpaid: European Society of Medical Oncology; Non-Financial Interests, Leadership Role, Foundation Council Member, Unpaid: European Thoracic Oncology Platform; Non-Financial Interests, Advisory Role, Mesothelioma Committee, Unpaid: International Association for the Study of Lung Cancer; Non-Financial Interests, Member of Board of Directors, Unpaid: Mesothelioma Applied Research Foundation; Non-Financial Interests, Advisory Role, Honorary Clinical Advisor, Unpaid: ALK Positive UK; Non-Financial Interests, Advisory Role, Research Advisory Group Member, Unpaid: Ruth Strauss Foundation; Non-Financial Interests, Advisory Role, Scientific Advisory Board Member, Unpaid: Lung Cancer Europe. All other authors have declared no conflicts of interest.