Nintedanib plus pemetrexed versus placebo plus pemetrexed in patients with relapsed or refractory, advanced non-small cell lung cancer (LUME-Lung 2): A randomized, double-blind, phase III trial

Nasser H. Hanna, Rolf Kaiser, Richard N. Sullivan, Osvaldo Rudy Aren, Myung Ju Ahn, Beatrice Tiangco, Isabelle Voccia, Joachim von Pawel, Vladimir Kovcin, Jason Agulnik, Birgit Gaschler-Markefski, José Barrueco, Patricia Sikken, Charles Schloss, Joo Hang Kim

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Objectives LUME-Lung 2 investigated the efficacy/safety of nintedanib plus pemetrexed in patients with pretreated non-squamous non-small cell lung cancer (NSCLC). Materials and methods Patients with stage IIIB/IV or recurrent non-squamous NSCLC who had received one prior chemotherapy regimen were randomized (1:1 stratified by histology [adenocarcinoma/non-adenocarcinoma], prior bevacizumab, Eastern Cooperative Oncology Group performance status and presence of brain metastases) to receive intravenous pemetrexed 500 mg/m2 on Day 1 plus nintedanib 200 mg orally twice daily or matching placebo on Days 2–21, every 3 weeks until progression/unacceptable toxicity. Progression-free survival (PFS) by independent central review was the primary endpoint. Overall survival (OS) was the key secondary endpoint. Results Based on the pre-planned futility analysis of investigator-assessed PFS, conducted by an independent data monitoring committee, recruitment was halted on 18 June 2011 after 713 (n = 353 nintedanib/pemetrexed; n = 360 placebo/pemetrexed)/1300 planned patients had enrolled. There were no safety concerns. Subsequent analysis demonstrated a significant improvement in PFS favoring nintedanib/pemetrexed over placebo/pemetrexed (median 4.4 months vs 3.6 months; hazard ratio [HR] = 0.83, 95% confidence interval [CI] 0.70–0.99, p = 0.0435). There was no significant difference in OS (median 12.0 months vs 12.7 months; HR = 1.01, 95% CI 0.85–1.21, p = 0.8940) after 514 deaths. Nintedanib/pemetrexed resulted in a higher incidence of grade ≥3 elevated alanine aminotransferase (23.3% vs 7.3%), elevated aspartate aminotransferase (12.1% vs 1.7%) and diarrhea (3.5% vs 1.1%) compared with placebo/pemetrexed, but no difference in hypertension, bleeding or thrombosis. Conclusion Although recruitment stopped prematurely, combining nintedanib with pemetrexed significantly prolonged PFS in patients with advanced non-squamous NSCLC after first-line chemotherapy, with a manageable safety profile.

Original languageEnglish (US)
Pages (from-to)65-73
Number of pages9
JournalLung Cancer
Volume102
DOIs
StatePublished - Dec 1 2016

Keywords

  • Angiogenesis inhibitor
  • Nintedanib
  • Non-small cell lung cancer
  • Phase III
  • Second-line

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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    Hanna, N. H., Kaiser, R., Sullivan, R. N., Aren, O. R., Ahn, M. J., Tiangco, B., Voccia, I., Pawel, J. V., Kovcin, V., Agulnik, J., Gaschler-Markefski, B., Barrueco, J., Sikken, P., Schloss, C., & Kim, J. H. (2016). Nintedanib plus pemetrexed versus placebo plus pemetrexed in patients with relapsed or refractory, advanced non-small cell lung cancer (LUME-Lung 2): A randomized, double-blind, phase III trial. Lung Cancer, 102, 65-73. https://doi.org/10.1016/j.lungcan.2016.10.011