Nintedanib plus Pemetrexed Prolongs PFS in Advanced Lung Cancer

CHICAGO―Adding the angiokinase inhibitor nintedanib (N) to pemetrexed (PEM) is associated with improved progression-free survival (PFS) times among patients diagnosed with non-squamous non-small cell lung cancer (NSCLC) for whom first-line chemotherapy has failed, according to results from the randomized, double-blind, multicenter phase 3 LUME-Lung 2 trial, reported at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting.

“Treatment with N+PEM significantly improved centrally reviewed PFS versus placebo plus PEM in patients with advanced non-squamous NSCLC previously treated with chemotherapy, and has a manageable safety profile,” reported Nasser H. Hanna, MD of the Melvin and Bren Simon Cancer Center at Indiana University, in Indianapolis, IN, and an international team of coauthors.

Nintedanib is an oral small-molecule targeted agent that inhibits vascular endothelial growth factor receptor (VEGFR) 1-3, fibroblast growth factor receptor (FGFR) 1-3, and platelet-derived growth factor receptor (PDGFR) α and β, RET, and Fit3.

Study participants were randomly assigned 1:1 to receive intravenous PEM 500 mg/m2 every 21 days with either 200 mg N orally twice per day (n=353) or placebo (n=360).

Patients in the N+PEM arm exhibited significantly superior PFS compared with patients who received placebo (median, 4.4 vs. 3.6 months; hazard ratio [HR], 0.83; 95% CI: 0.7-0.99; P=0.04), the coauthors reported. However, no differences in overall survival (median, 12.2 vs. 12.7 months; HR, 1.03; P=0.79) or response rate (9%) were identified, the authors cautioned.

Enrollment was halted following a planned data monitoring committee futility analysis of PFS, after randomly assigning 713 patients of 1,300 patients had enrolled, and participants were unblinded for on-protocol follow-up.

“The primary endpoint [PFS] was met even though the study was stopped prematurely,” Dr. Hanna noted. “Disease control was also significantly improved in N-treated patients (61% vs. 53%; odds ratio, 1.37; P=0.039).”

Nintedanib was associated with a higher incidence of grade 3+ elevations in alanine aminotransferase (23% vs. 7%) and aspartate aminotransferase (12% vs. 2%), as well as diarrhea (3% vs. 1%), the coauthors reported.