Science and Research

Change in non-small-cell lung cancer tumor size in patients treated with nintedanib plus docetaxel: analyses from the Phase III LUME-Lung 1 study

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 adenocar-cinoma population, including in patients with the poorest prognosis due to aggressive tumor dynamics.
  • Reck, M.
  • Mellemgaard, A.
  • Novello, S.
  • Postmus, P. E.
  • Gaschler-Markefski, B.
  • Kaiser, R.
  • Buchner, H.

Keywords

  • adenocarcinoma
  • non-small-cell lung cancer
  • squamous cell carcinoma
  • sum of longest diameters
  • surrogate OS endpoints
  • tumor burden
  • Hoffmann-La Roche, Eli Lilly, Merck Sharp & Dohme Limited (MSD), Bristol-Myers
  • Squibb (BMS), AstraZeneca, Celgene, Merck and Pfizer, outside the submitted work
  • Anders Mellemgaard reports personal fees from advisory boards from Boehringer
  • Ingelheim, MSD, and Eli Lilly and as a speaker from Boehringer Ingelheim, outside
  • the submitted work
  • Silvia Novello reports personal fees (Speaker Bureau) from
  • MSD, BMS, Eli Lilly, AstraZeneca, and Roche, outside the submitted work. Pieter
  • Postmus reports personal fees from advisory boards from Boehringer Ingelheim
  • (during the conduct of the study), AstraZeneca, AbbVie, BMS, Eli Lilly, Janssen,
  • G1 Therapeutics, MSD, Novartis, and Roche, outside the submitted work
  • Birgit
  • Gaschler-Markefski is an employee of Boehringer Ingelheim
  • Rolf Kaiser is an
  • employee of Boehringer Ingelheim and reports a patent issued (EP 2994125)
  • and
  • Hannes Buchner reports personal fees from Boehringer Ingelheim during the conduct
  • of the study. The authors report no other conflicts of interest in this work.
Publication details
DOI: 10.2147/OTT.S170722
Journal: OncoTargets and therapy
Pages: 4573-4582 
Work Type: Original
Location: ARCN
Disease Area: LC
Partner / Member: Ghd
Access-Number: 30122949
See publication on PubMed

DZL Engagements

chevron-down