Effect of Nintedanib (Bibf 1120) Combined with Standard 2Nd-Line Docetaxel in Nsclc Patients Who Received Prior Pemetrexed in Lume-Lung 1: a Randomised, Placebo-Controlled Phase III Trial

Aim: Nintedanib (N) is an oral, triple angiokinase inhibitor of VEGF, PDGF and FGF signalling. Primary analysis of the LUME-Lung 1 trial (NCT00805194; 1199.13) showed a significant improvement in PFS with N + docetaxel (D) in NSCLC patients (pts) regardless of histology; OS was also significantly improved in adenocarcinoma (adeno) pts. Pemetrexed (PEM) is a standard 1st-line and maintenance treatment for nonsquamous NSCLC pts. To determine whether prior PEM would influence outcomes of pts in LUME-Lung 1, we evaluated the efficacy and safety of N + D in pts who received 1st-line and maintenance PEM. Methods: 1314 pts with Stage IIIB/IV recurrent NSCLC were randomised to receive either N 200 mg bid + D 75 mg/m2 q21d (n = 655) or placebo (Pl) + D (n = 659) in LUME-Lung 1. Retrospective subgroup analyses according to prior PEM treatment (1st line or maintenance) were performed to determine OS and safety. Results: The percentage of pts with adeno tumour histology who were treated 1st line with PEM along with platinum was approximately 19% (N arm, n = 61; Pl arm, n = 65). Pt characteristics were balanced across groups. OS results according to receipt of any PEM 1st-line and maintenance therapy for adeno pts are shown in the table. For all pts and those with adeno histology in particular, no significant difference in OS was noted between those who did or did not receive PEM; no significant interaction between treatment groups and any PEM treatment was observed. Further, slightly more pts in the N arms across all subgroups experienced grade ≥3 adverse events; diarrhoea and reversible increases in liver enzymes occurred more frequently in pts in both N arms. OS results in NSCLC pts with adeno histology who received 1st-line and/or maintenance PEM No PEM 1st-line PEM 1st-line No maintenance PEM 1st-line Maintenance PEM 1st-line N n = 261 Pl n = 271 N n = 61 Pl n = 65 N n = 309 Pl n = 322 N n = 13 Pl n = 14 Median OS, months 13.4 10.8 12.0 8.0 12.6 10.0 18.9 12.8 HR (95% CI); p-value 0.83 (0.68–1.00); p = 0.05 0.79 (0.53–1.18); p = 0.25 0.84 (0.70–1.00); p = 0.05 0.78 (0.30–2.07); p = 0.62 Interaction between treatment & subgroup variable, p-value p = 0.9026 p = 0.7162 Conclusions: On-study treatment with N + D resulted in a comparably favourable improvement in OS regardless of whether pts with adeno tumours were treated 1st line with a PEM- or non-PEM-containing platinum doublet. Disclosure: A. Mellemgaard: Advisory Board: Boehringer Ingelheim; J. von Pawel: Advisory Board/Consultant: AbbVie, Clovis, Daiichi Sankyo, Novartis, Pfizer, Vertex Pharmaceuticals; J. Barrueco: Employee: Boehringer Ingelheim Pharmaceuticals Inc., USA; H. Buchner, J. Hocke and R. Kaiser: Employee: Boehringer Ingelheim Pharma GmbH KG, Germany;S. Novello: Advisory Board/Honoraria/Invited Speaker: AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Roche; J. Douillard: Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Merck Serono, Roche; Educational Symposia: Amgen, AstraZeneca, Bayer; Research Grants: Merck Serono; M. Reck: Advisory Board: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Hoffmann-la Roche, Lilly, Novartis, Pfizer. All other authors have declared no conflicts of interest.