473P - Prior taxane use in the LUME-Lung 1 phase III trial and the effect on outcome following 2nd-line treatment with nintedanib (BIBF 1120) and docetaxe...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anticancer Agents
Non-Small Cell Lung Cancer
Biological Therapy
Presenter Maciej Krzakowski
Citation Annals of Oncology (2014) 25 (suppl_4): iv146-iv164. 10.1093/annonc/mdu331
Authors M. Krzakowski1, A. Mellemgaard2, S. Orlov3, J. von Pawel4, M. Gottfried5, I. Bondarenko6, M. Liao7, J. Barrueco8, B. Gaschler-Markefski9, R. Kaiser10, S. Novello11, J. Douillard12, M. Reck13
  • 1Lung & Thoracic Tumours, The Maria Sklodowska-Curie Institute of Oncology, 02-781 - Warsaw/PL
  • 2Oncology, Herlev University Hospital, 2730 - Herlev/DK
  • 3Thoracic Oncology, St Petersburg State Medical University, St. Petersburg/RU
  • 4Pneumology Clinic, Asklepios Fachkliniken, DE-82131 - Gauting/DE
  • 5Lung Cancer Unit, Meir Medical Center, IL-44281 - Kfar Saba/IL
  • 6Oncology, Dnepropetrovsk Medical Academy, City Clinical Hospital #4, 49044 - Dnepropetrovsk/UA
  • 7Lung Tumor, Shanghai Chest Hospital, Shanghai/CN
  • 8Medical, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield/US
  • 9Global Biometry & Clin. Applications, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach/DE
  • 10Medical, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach/DE
  • 11Oncology, University of Turin, 10043 - Turin/IT
  • 12Medical Oncology, Centre René Gauducheau, Nantes/FR
  • 13Thoracic Oncology, Lung Clinic Grosshandorf, 22927 - Grosshansdorf/DE



Several Phase III studies confirm the efficacy of standard 2nd-line docetaxel (D) in advanced non-small cell lung cancer (NSCLC) patients (pts) previously treated with 1st-line paclitaxel-based therapy irrespective of tumour histology. In LUME-Lung 1, nintedanib (N)—an oral, triple angiokinase inhibitor of VEGF, PDGF and FGF signalling—has demonstrated clinically meaningful efficacy along with 2nd-line chemotherapy (NCT00805194; 1199.13). Here we report the efficacy and safety of N + D in pts previously treated with taxanes as part of a preplanned analysis.


Stage IIIB/IV recurrent NSCLC pts (N = 1314) progressing after 1st-line chemotherapy were randomised 1:1 to receive either N 200 mg bid + D 75 mg/m2 q21d (n = 655) or placebo (Pl) + D (n = 659). Endpoints evaluated included progression-free survival (PFS) by central independent review, overall survival (OS) and safety. Chemotherapy with 1st-line D was an exclusion criterion; subgroup analyses according to the pt's use of 1st-line taxane therapy and NSCLC histology were also performed.


Pt characteristics were balanced across all groups. For all pts and those with adenocarcinoma (Ad) in particular, no significant difference in survival benefit was noted regardless of the use of 1st-line taxane therapy (Table). Comparison of N + D and Pl + D showed that the percentage of all pts with grade ≥3 adverse events (AEs) was slightly higher for pts in the N arm (no 1st-line taxane = 71.6% vs 65.5%; prior 1st-line taxane = 70.3% vs 59.4%). Consistent with overall findings in LUME-Lung 1, reversible increases in alanine and aspartate aminotransferases as well as diarrhoea were the AEs that were more common among all pts in the N arm.

OS results for LUME-Lung 1 in NSCLC pts who received 1st-line taxane therapy

All pts Pts with Ad
No taxane 1st-line Taxane 1st-line No taxane 1st-line Taxane 1st-line
N, n = 510 Pl, n = 519 N, n = 145 Pl, n = 140 N, n = 245 Pl, n = 271 N, n = 77 Pl, n = 65
Median OS, months 10.0 9.1 11.5 9.0 12.2 10.3 15.1 11.6
HR (95% CI); p-value 0.97 (0.85–1.11); p = 0.67 0.81 (0.62–1.06); p = 0.13 0.86 (0.71–1.05); p = 0.13 0.75 (0.51–1.11); p = 0.15
Interaction between treatment & subgroup variable, p-value p = 0.2562 p = 0.6135


On-study treatment with N + D resulted in a comparably favourable OS improvement regardless of whether pts with tumours of Ad histology were treated 1st line with a taxane- or non-taxane-containing platinum doublet.


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; B. Gaschler-Markefski 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.