1618PD - Overall survival (OS) and forced vital capacity (FVC) results from the LUME-Meso study of nintedanib (N) + pemetrexed/cisplatin (PEM/CIS) vs placeb...

Date 11 September 2017
Event ESMO 2017 Congress
Session Non-metastatic NSCLC and other thoracic malignancies
Topics Anti-Cancer Agents & Biologic Therapy
Mesothelioma
Lung and other Thoracic Tumours
Presenter Silvia Novello
Citation Annals of Oncology (2017) 28 (suppl_5): v568-v572. 10.1093/annonc/mdx389
Authors S. Novello1, A.K. Nowak2, F. Grosso3, N. Steele4, S. Popat5, L. Greillier6, T. John7, N.B. Leighl8, M. Reck9, N. Pavlakis10, J.B. Sorensen11, D. Planchard12, G.L. Ceresoli13, B. Hughes14, J. Mazieres15, M.A. Socinski16, U. von Wangenheim17, J. Barrueco18, N. Morsli19, G. Scagliotti20
  • 1Department Of Oncology, University of Turin, S. Luigi Hospital, 10124 - Torino/IT
  • 2School Of Medicine, Faculty Of Medicine And Health Sciences, University of Western Australia, Crawley/AU
  • 3Department Of Oncology, SS Antonio e Biagio Hospital, Alessandria/IT
  • 4-, The Beatson West of Scotland Cancer Centre, Glasgow/GB
  • 5-, Royal Marsden Hospital NHS Foundation Trust, SW3 6JJ - London/GB
  • 6Assistance Publique - Hopitaux De Marseille, Aix Marseille University, 13915 - Marseille/FR
  • 7Olivia Newton John Cancer Research Institute, Austin Hospital, Heidelberg/AU
  • 8-, Princess Margaret Cancer Centre, Toronto/CA
  • 9Department Of Thoracic Oncology, Lung Clinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), 22927 - Grosshansdorf/DE
  • 10Northern Cancer Institute, St Leonard's, Sydney/AU
  • 11-, Rigshospitalet, Copenhagen/DK
  • 12Department Of Medical Oncology, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 13Department Of Oncology, Cliniche Humanitas Gavazzeni, 24125 - Bergamo/IT
  • 14-, The Prince Charles Hospital, Chermside/AU
  • 15-, HOP Larrey, Onco, Toulouse/FR
  • 16-, University of Pittsburgh, Pittsburgh/US
  • 17-, Boehringer Ingelheim GmbH & Co. KG, Biberach/DE
  • 18-, Boehringer Ingelheim Pharmaceuticals, Inc., 06877 - Ridgefield/US
  • 19-, Boehringer Ingelheim France S.A.S., Paris/FR
  • 20Department Of Oncology, University of Turin, S. Luigi Hospital, Torino/IT

Abstract

Background

N targets MPM by inhibiting VEGFR 1–3, PDGFR α/β, FGFR 1–3, Src and Abl kinases. In a Phase II/III, double-blind, randomised LUME-Meso trial, primary Phase II analysis showed improved progression-free survival (PFS) with N and a trend for prolonged interim OS. FVC, a common pulmonary function test reflecting pt performance and quality-of-life, was also evaluated.

Methods

Pts with unresectable MPM (ECOG PS 0–1), stratified by histology, were randomised 1:1 to ≤ 6 cycles PEM (500 mg/m2)/CIS (75 mg/m2, Day 1) + N or P (200 mg bid, Days 2–21), followed by N/P monotherapy until progression/unacceptable toxicity. The primary endpoint was PFS; OS was the secondary endpoint. FVC was a further endpoint, evaluated as percentage change from baseline for cycle (C)1–8 using a mixed-effect model with repeated measures.

Results

87 pts were randomised (N = 44; P = 43). At the primary OS analysis (71% of events), OS benefit favoured N (hazard ratio [HR]=0.77; 95% confidence interval [CI]: 0.46–1.29; p = 0.319) and primary PFS results were confirmed (HR = 0.54; [95% CI]: 0.33–0.87; p = 0.010). Benefit of N was greatest in epithelioid MPM for PFS (HR = 0.49; 95% CI: 0.30–0.82; p = 0.006; median [m] 9.7 vs 5.7 months [mo]) and OS (HR = 0.70; 95% CI: 0.40–1.21; p = 0.197; mOS 20.6 vs 15.2 mo). Adjusted mean (standard error [SE]) FVC change at C8 favoured N over P (all pts: +10.0 [SE: 3.5]% vs + 2.8 [SE: 3.7]%; mean treatment difference [TD]: 7.2 [SE: 4.5]%; pts with epithelioid histology: +14.1 [SE: 2.9]% vs + 4.2 [SE: 3.3]%; mean TD: 9.9 [SE 4.5]%). A trend towards improved FVC with N over P was observed from C2 in all pts and epithelioid histology. Neutropenia was the most frequent Grade ≥3 adverse event (AE; N, 43%; P, 12%); febrile neutropenia rate was low (4.5 vs 0%). AEs leading to discontinuation were lower with N than P (7 vs 17%).

Conclusions

Addition of N to PEM/CIS resulted in a substantial improvement in PFS, a trend for prolonged OS and improvement in the pulmonary function measure FVC. Treatment effect was most pronounced in pts with epithelioid histology; Phase III is recruiting in this population (NCT01907100).

Clinical trial identification

NCT01907100

Legal entity responsible for the study

Boehringer Ingelheim Pharma GmbH & Co. KG

Funding

Boehringer Ingelheim Pharma GmbH & Co. KG

Disclosure

S. Novello: Honoraria from Roche, Boehringer Ingelheim, Bristol-Meyers Squibb, Eli Lilly, AstraZeneca, Pfizer and Novartis; payment as a consultant from Roche, A.K. Nowak: Payment as consultant from Aduro Biotech, Morphotek, Bayer, AstraZeneca, Sellas Life Sciences, Trizell, Boehringer-Ingelhelm, Epizyme, Roche; travel expenses by Amgen and AstraZeneca; received research funding from Boehringer-Ingelhelm and AstraZeneca. F. Grosso: Travel expenses paid by Boehringer-Ingelhelm and PharmaMar. N. Steele: Honoraria from Pfizer, Novartis; payment as consultant from MSD, Boehringer-Ingelhelm and BMS; travel expenses paid by Pfizer, MSD, Boehringer-Ingelhelm and research funding from Merck Serono, AstraZeneca, Boehringer-Ingelhelm, BMS, Novartis and Roche. S. Popat: Honoraria from Pfizer, Boehringer-Ingelheim (BI), AstraZeneca, Roche, Eli-Lilly, Novartis; payment as consultant from Boehringer-Ingelheim, Roche, Eli-Lilly, Novartis, Pfizer; received funding from BI, Epizyme, BMS, Clovis Oncology, Roche and Eli-Lily. L. Greillier: Honoraria from Roche, Boehringer Ingelheim, BMS, Eli Lilly, AstraZeneca, Pfizer and Novartis; payment as a consultant from Roche, Boehringer Ingelheim and BMS; author’s institution has received research funding from Roche. T. John: Honoraria from Roche, Lilly, BMS, AstraZeneca/MedImmune, Pfizer; payment as consultant from AstraZeneca, AstraZeneca/MedImmune, Pfizer, Roche/Genentech and travel expenses paid by Boehringer-Ingelhelm, Roche and AstraZeneca. N.B. Leighl: Travel expenses paid for by AstraZeneca, MSD, BMS and Pfizer and has received research funding from Novartis. M. Reck: Honoraria, consultation payment and speakers bureau attendance from Boehringer-Ingelhelm, Roche, Eli-Lily, Proacta, AstraZeneca, BMS, MSD, Merck, Novartis, Pfizer and Celgene. N. Pavlakis: Honoraria and payment as consultant from Specialised Therapeutics, Pfizer, Boehringer-Ingelhelm, Merck Serono, Bayer, AstraZeneca, Novartis, Roche, AMtene. Author has also been paid to consult with Sanofi. J.B. Sorensen: Payment as consultant from Roche, Merck, Boehringer-Ingelhelm and Eli-Lilly. D. Planchard: Payment as consultant from Lilly, Boehringer-Ingelhelm, BMS, Pfizer, Clovis Oncology, MSD, Sanofi, AstraZeneca, Novartis and Roche and has received research funding from Novartis. G.L. Ceresoli: Research funding from Bayer. B. Hughes: Payment as consultant from MSD, BMS and Roche and has received travel expenses from MSD. J. Mazieres: Research funding received from BMS and Roche. M.A. Socinski: Honoraria and payment for consultation from Genetech and their institution has received funding from Pfizer. U. von Wangenheim, J. Barrueco, N. Morsli: Employed by Boehringer Ingelhelm. G. Scagliotti: Honoraria from Eli-Lily, AstraZeneca, Roche, Pfizer, MSD; payment as consultant from Eli-Lily; travel expenses by Bayer and has been paid by Eli-Lily and MSD to participate in a Speaker’s Bureau.