Nintedanib is a triple angiokinase inhibitor which blocks kinase activity at vascular endothelial growth factor receptors (VEGFR 1-3), platelet-derived growth factor receptors (PDGFR α and β) and fibroblast growth factor receptors (FGFR 1-3).
Licensing approval for Vargatef was based on the results of the phase III which involved 1,314 adults with locally advanced, metastatic or recurrent NSCLC after one prior line of chemotherapy, including 658 patients with adenocarcinoma.
Patients were randomised to receive nintedanib 200mg (n=655) or placebo (n=659) orally twice daily in combination with intravenous docetaxel 75mg/m2 every 21 days.
The addition of nintedanib to docetaxel therapy resulted in a significant reduction in the risk of progression or death of 21% for the overall population (hazard ratio [HR] 0.79, p=0.0019) and 23% for the adenocarcinoma population (HR 0.77, p=0.0193).
Nintedanib plus docetaxel also significantly improved overall survival in the adenocarcinoma population with a 17% reduction in the risk of death (HR 0.83, p=0.0359) and a median overall survival improvement of 2.3 months versus placebo (12.6 months vs 10.3 months, p=0.0359). The overall survival difference in the total study population did not reach significance.
The most commonly reported adverse effects specific for nintedanib were diarrhoea, raised liver enzymes and vomiting. However, the effect of these on self-reported quality of life were not sufficient to affect the overall treatment benefit observed in the study.