Adding nintedanib, an oral triple angiokinase inhibitor, to second-line pemetrexed significantly prolonged progression-free survival compared with pemetrexed alone among patients with advanced non-squamous non-small cell lung cancer (NSCLC) who had received first-line chemotherapy, according to a study published in Lung Cancer.1

Nintedanib is approved in Europe in combination with docetaxel for the treatment of adult patients with locally advanced, metastatic, or locally recurrent non-small cell lung adenocarcinoma after first-line chemotherapy. Approval was based on findings from the LUME-Lung 1 trial.

To evaluate the efficacy and safety of second-line nintedanib plus pemetrexed in patients with pretreated non-squamous NSCLC, investigators conducted the phase 3 LUME-Lung 2 ( Identifier: NCT00806819). For the double-blind study, researchers planned to enroll 1300 patients with stage IIIB/IV or recurrent non-squamous NSCLC who had received 1 prior chemotherapy regimen.

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Participants were randomly assigned 1:1 to receive pemetrexed intravenously on day 1 plus nintedanib orally twice daily or placebo on days 2 to 21 of each 3-week cycle until disease progression or unacceptable toxicity.

Pre-planned futility analysis of investigator-assessed progression-free survival led to a recruitment halt after the enrollment of 713 patients. The authors report no safety concerns.

Subsequent analyses showed that nintedanib significantly reduced the risk of progression or death by 17% compared with pemetrexed alone (hazard ratio [HR], 0.83; 95% CI, 0.70-0.99; P = .0435). Median progression-free survival was 4.4 months with the combination vs 3.6 months with single-agent pemetrexed.

Researchers observed no significant difference in overall survival between the 2 treatment arms (HR, 1.01; 95% CI, 0.85-1.21; P = .8940). Median overall survival was 12.0 months and 12.7 months for nintedanib and placebo, respectively.

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Nintedanib plus pemetrexed was associated with a higher incidence of grade 3 or higher elevated alanine transaminase (ALT) and aspartate transaminase (AST) and diarrhea compared with pemetrexed plus placebo. There were no differences in the incidences of hypertension, bleeding, or thrombosis.                  


  1. Hanna NH, Kaiser R, Sullivan RN, et al. 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. In press.