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 (ClinicalTrials.gov 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.
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.
- 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.