Martin Reck,1 Anders Mellemgaard,2 Silvia Novello,3 Pieter E Postmus,4 Birgit Gaschler-Markefski,5 Rolf Kaiser,5,6 Hannes Buchner7



1Department of Thoracic Oncology, Lung Clinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany; 2Department of Internal Medicine and Oncology, Bornholms Hospital, Ronne, Denmark; 3Department of Oncology, University of Turin, S. Luigi Hospital, Torino, Italy; 4Leiden University Medical Center, Leiden, the Netherlands; 5Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany; 6Institute of Pharmacology, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany; 7Staburo GmbH, Munich, Germany



Background: Nintedanib in combination with docetaxel is approved in the European Union and other countries for the treatment of patients with advanced non-small-cell lung cancer (NSCLC) of adenocarcinoma histology after first-line chemotherapy, based on the overall survival findings of Phase III LUME-Lung 1 study. Change in target lesion size over time as a treatment effect was assessed in patients from this study.

Methods: Tumor size was evaluated using predefined tumor measurements. Mixed-effects models were used to quantify individual relationships between time from randomization and tumor burden, measured as the sum of longest diameter (SLD) of target lesions and assessed by an independent review (Response Evaluation Criteria In Solid Tumors [RECIST] v1.0). Exploratory analyses were conducted on the overall adenocarcinoma population, adenocarcinoma patients with time from start of first-line therapy <9 months (TSFLT <9), adenocarcinoma patients who had progressive disease as best response to first-line therapy (PD-FLT), and in squamous cell carcinoma patients.

Results: Estimated mean baseline SLD was 82.5 mm in the adenocarcinoma (n=658), 88.3 mm in the TSFLT <9 (n=405), 98.1 mm in the PD-FLT (n=117), and 94.3 mm in the squamous cell carcinoma (n=555) populations. Treatment with nintedanib/docetaxel showed a significant reduction in tumor size over time (P<0.0001) in patients with adenocarcinoma compared with placebo/docetaxel, and in patients with squamous cell carcinoma (P=0.0049). Treatment difference at 6 months was 9.7 mm in the overall adenocarcinoma population, 16.8 mm in the TSFLT <9 population, 19.7 mm in the PD-FLT population, and 6.8 mm in the squamous cell carcinoma population. SLD at 2 months post-randomization was identified as a surrogate endpoint for overall survival, in addition to progression-free survival, for all except the PD-FLT population.

Conclusion: Treatment with nintedanib/docetaxel significantly decreased tumor burden and decelerated tumor size over time compared with placebo/docetaxel in the overall adenocarcinoma population, including in patients with the poorest prognosis due to aggressive tumor dynamics.



Keywords: adenocarcinoma, non-small-cell lung cancer, sum of longest diameters, surrogate OS endpoints, squamous cell carcinoma, tumor burden

