Efficacy and safety of nintedanib (NIN)/docetaxel (DOC) in patients with lung adenocarcinoma: Further analyses from the LUME-Lung 1 study

Background

NIN is a triple angiokinase inhibitor approved in the EU in combination with DOC for the treatment of adenocarcinoma non-small cell lung cancer patients after first-line therapy (FLT). A continuous linear correlation between overall survival (OS) benefit with NIN and the predictive marker “time from start of FLT” (TSFLT) has been observed in adenocarcinoma patients.

Methods

First, analyses were conducted of European adenocarcinoma patients, who comprise the majority of the population from the Phase III LUME-Lung 1 trial comparing NIN/DOC with placebo (PLA)/DOC (NCT00805194). Second, in order to further characterise time from FLT, analyses were conducted in adenocarcinoma populations defined by the dichotomisation at appropriate cut-points of TSFLT or progressive disease (PD) as best response to FLT. Analyses based on “time from end of FLT” (TEFLT) as described in other clinical trials were also performed.

Results

In the overall adenocarcinoma population (n = 658), both independently assessed progression-free survival (median 4.0 vs 2.8 months, hazard ratio [HR] 0.77 [95% CI 0.6–0.96]; p = 0.0193) and OS were significantly longer with NIN/DOC vs PLA/DOC (median OS [mOS] 12.6 vs 10.3 months, HR 0.83 [95% CI 0.70–0.99]; p = 0.0359). OS improved both in the overall European adenocarcinoma (n = 463; mOS 13.4 vs 8.7 months, HR 0.79 [0.65–0.97]; p = 0.0254) and in European adenocarcinoma patients with TSFLT 

Conclusions

NIN plus DOC exhibits significant OS benefits in the adenocarcinoma population and a more pronounced OS benefit in patients with a shorter time since FLT and more aggressive tumours.

Clinical trial identification

NCT00805194

Legal entity responsible for the study

Boehringer Ingelheim GmbH & Co. KG

Funding

Boehringer IngelheimGmbH & Co. KG

Disclosure

D. Heigener: Honoraria and travel reimbursements from Boehringer Ingelheim. Honoraria from Eli Lilly, Roche, Pfizer and BMS and non-financial funding from Boehringer Ingelheim during the conduct of this study. M. Gottfried: Non-financial support from Boehringer lngelheim during the conduct of the study. J. Bennouna: Personal fees from Roche, Astra-Zeneca and Boehringer Ingelheim and non-financial support from Boehringer Ingelheim in the conduct of this study. I. Bondarenko: Non-financial support from Boehringer Ingelheim during the conduct of this study. J-Y. Douillard: Personal fees from Boehringer Ingelheim, Astra Zeneca and NEKTAR. Non-financial funding from Boehringer Ingelheim. His institute receives grants from Merck Serono. M. Krzakowski: Honoraria from Boehringer Ingelheim, Merck, BMS and Roche and non-financial support from Boehringer Ingelheim. A. Mellemgaard: Honoraria from Boehringer Ingelheim. Non financial support during the conduct of this study from Boehringer Ingelheim. S. Novello: Honoraria from Boehringer Ingelheim, Eli Lilly, Roche, Astra-Zeneca and MSD. Non-financial support from Boehringer Ingelheim during the conduct of this study. S. Orlov: Non-financial funding from Boehringer Ingelheim during the conduct of this study. Y.J. Summers: Honoraria and non-financial funding from Boehringer Ingelheim. J. von Pawel: Non-financial support from Boehringer Ingelheim. J. Hocke, R. Kaiser: Employee of Boehringer Ingelheim. M. Reck: Non-financial support from Boehringer lngelheim. Honoraria from Boehringer lngelheim, Roche, Eli Lilly, MSD, BMS, AstraZeneca, Pfizer, and Novartis.