J Clin Oncol 2017 Nov 11;35(31):3591-3600. Epub 2017 Sep 11.
Federica Grosso, Azienda Ospedaliera SS Antonio e Biagio General Hospital, Alessandria; Silvia Novello and Giorgio Scagliotti, L'università di Torino, Azienda Sanitaria Ospedale San Luigi Gonzaga, Turin, Italy; Anna K. Nowak, University of Western Australia, Crawley, and Sir Charles Gairdner Hospital, Nedlands, Western Australia; Thomas John, Olivia Newton-John Cancer Research Institute, Austin Hospital, Heidelberg, Victoria, Australia; Sanjay Popat, The Royal Marsden Hospital National Health Service (NHS) Foundation Trust, London; Nicola Steele, The Beatson West of Scotland Cancer Centre, Glasgow; Paul Taylor, University Hospitals of South Manchester NHS Trust, Wythenshawe, Manchester, United Kingdom; Laurent Greillier, Assitance Publique Hôpitaux de Marseille, Aix Marseille University, Marseille; David Planchard, Institut Gustave Roussy, Villejuif; Nassim Morsli, Boehringer Ingelheim France S.A.S., Paris, France; Natasha B. Leighl, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Martin Reck, Lung Clinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf; Ute von Wangenheim, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany; Jens Benn Sørensen, Rigshospitalet - Finsencentret, Copenhagen, Denmark; Mark A. Socinski, Florida Hospital Cancer Institute, Orlando, FL; Arsène Bienvenu Loembé, Boehringer Ingelheim B.V., Alkmaar, the Netherlands; and José Barrueco, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT.
Purpose LUME-Meso is a phase II/III randomized, double-blind trial designed to assess efficacy and safety of nintedanib plus chemotherapy as first-line treatment of malignant pleural mesothelioma (MPM). Phase II results are reported here. Patients and Methods Chemotherapy-naïve patients with unresectable, nonsarcomatoid MPM (Eastern Cooperative Oncology Group performance status 0 to 1), stratified by histology (epithelioid or biphasic), were randomly assigned in a 1:1 ratio to up to six cycles of pemetrexed and cisplatin plus nintedanib (200 mg twice daily) or placebo followed by nintedanib plus placebo monotherapy until progression. The primary end point was progression-free survival (PFS). Results Eighty-seven patients were randomly assigned. The median number of pemetrexed and cisplatin cycles was six; the median treatment duration for nintedanib was 7.8 months and 5.3 months for placebo. Primary PFS favored nintedanib (hazard ratio [HR], 0.56; 95% CI, 0.34 to 0.91; P = .017), which was confirmed in updated PFS analyses (HR, 0.54; 95% CI, 0.33 to 0.87; P = .010). A trend toward improved overall survival also favored nintedanib (HR, 0.77; 95% CI, 0.46 to 1.29; P = .319). Benefit was evident in epithelioid histology, with a median overall survival gain of 5.4 months (HR, 0.70; 95% CI, 0.40 to 1.21; P = .197; median [nintedanib v placebo], 20.6 months v 15.2 months) and median PFS gain of 4.0 months (HR, 0.49; 95% CI, 0.30 to 0.82; P = .006; median [nintedanib v placebo], 9.7 v 5.7 months). Neutropenia was the most frequent grade ≥ 3 adverse event (AE; nintedanib 43.2% v placebo 12.2%); rates of febrile neutropenia were low (4.5% in nintedanib group v 0% in placebo group). AEs leading to discontinuation were reported in 6.8% of those receiving nintedanib versus 17.1% of those in the placebo group. Conclusion Addition of nintedanib to pemetrexed plus cisplatin resulted in PFS improvement. AEs were manageable. The clinical benefit was evident in patients with epithelioid histology. The confirmatory phase III part of the study is ongoing.