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. (December 2016)

• Record Type: Journal Article
• Authors: Hanna, Nasser H.; Kaiser, Rolf; Sullivan, Richard N.; Aren, Osvaldo Rudy; Ahn, Myung-Ju; Tiangco, Beatrice; Voccia, Isabelle; Pawel, Joachim von; Kovcin, Vladimir; Agulnik, Jason; Gaschler-Markefski, Birgit; Barrueco, José; Sikken, Patricia; Schloss, Charles; Kim, Joo-Hang
• Is Part Of: Lung cancer. Volume 102(2016)
• Page Start: 65
• Page End: 73
• Publication Date: 2016-12
• Subjects: NSCLC non small cell lung cancer -- VEGF(R) vascular endothelial growth factor (receptor) -- PDGF(R) platelet-derived growth factor (receptor) -- FGR(R) fibroblast growth factor (receptor) -- PFS progression-free survival -- HR hazard ratio -- CI confidence interval -- OS overall survival -- RECIST response evaluation criteria in solid tumors -- ECOG PS Eastern Cooperative Oncology Group performance status -- CT computed tomography -- MRI magnetic resonance imaging -- AE adverse event -- CTCAE common toxicity criteria for adverse events -- QoL quality of life -- DMC data monitoring committee -- ITT intention-to-treat -- IQR interquartile range -- EGFR epidermal growth factor receptor -- ALK anaplastic lymphoma kinase; Angiogenesis inhibitor -- Phase III -- Nintedanib -- Non-small cell lung cancer -- Second-line; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2016.10.011
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Nintedanib plus docetaxel improved PFS for pretreated NSCLC compared with docetaxel in LUME-Lung 1. LUME-Lung 2 investigated nintedanib plus pemetrexed in pretreated non-squamous NSCLC. The trial was stopped early although did meet the primary endpoint (PFS). There were no safety concerns with the addition of nintedanib to pemetrexed. 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/m 2 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.