Nintedanib is a new triple angiokinase inhibitor that potently blocks the proangiogenic pathways mediated by
vascular endothelial growth factor receptors,
platelet-derived growth factor receptors, and
fibroblast growth factor receptors. Evidence about its efficacy in addition to second-line
chemotherapy in
non-small cell lung cancer (NSCLC) has been produced by two large randomized phase III clinical trials (LUME-Lung 1 and LUME-Lung 2), conducted in patients with pretreated NSCLC, without major risk factors for
bleeding. In the LUME-Lung 1, the addition of
nintedanib to
docetaxel significantly improved progression-free survival, which was the primary end point of the trial (3.4 vs. 2.7 months, hazard ratio: 0.79; p = 0.0019). Furthermore, a significant improvement in median overall survival (from 10.3 to 12.6 months) was observed in patients with
adenocarcinoma histology, with a greater advantage in patients who progressed within 9 months after start of first-line treatment (from 7.9 to 10.9 months) and in patients who were most refractory to first-line
chemotherapy (from 6.3 to 9.8 months). Adverse events were more common in the
docetaxel plus
nintedanib group, and they included
diarrhea and increased liver
enzymes, while no statistically significant increase in the incidence of
bleeding and
hypertension events by the addition of
nintedanib was observed. On these bases, the combination of
docetaxel and
nintedanib can be considered a new option for the second-line treatment for patients with advanced NSCLC with
adenocarcinoma histology. Future challenges are the identification of predictive factors to help the decision of using
nintedanib in eligible patients.