Currently, the US Food and Drug Administration–approved second-line treatments for non–small-cell lung cancer (NSCLC) include monotherapy with docetaxel (Taxotere), erlotinib (Tarceva), or pemetrexed (Alimta). A recent phase 3 clinical trial explored the safety and efficacy of nintedanib (Vargatef)—a potent oral angiokinase inhibitor—in combination with docetaxel, as a second-line treatment in patients with NSCLC (Reck M, et al. Lancet Oncol. 2014;15:143-155).
14 patients were randomized to receive nintedanib and docetaxel (ie, treatment group) or docetaxel and placebo (ie, placebo group). The primary end point was PFS, as assessed by central independent review. The key secondary end point was OS. The OS was assessed in the following order: first, in patients with adenocarcinoma who progressed within 9 months of starting first-line therapy; second, in all patients with adenocarcinoma; and third, in all patients, regardless of histology.
After a median follow-up of 7.1 months, the median PFS was 3.4 months in the treatment group compared with 2.7 months in the placebo group (P = .001). After a median follow-up of 31.7 months, the OS of patients with adenocarcinoma histology who progressed within 9 months of starting first-line therapy was 10.9 months versus 7.9 months in the placebo group (P = .007). Furthermore, in all patients with adenocarcinoma, the median OS was 12.6 months in the treatment group and 10.3 months in the placebo group (P = .035).
Although treatment with nintedanib plus docetaxel had a significant effect on OS in patients with adenocarcinoma histology who progressed within 9 months of first-line therapy and in all patients with adenocarcinoma, no difference in OS was found between the 2 groups when all patients were assessed independent of histology results.
AEs that were more common in the treatment group than in the placebo group included diarrhea, increases in alanine and in aspartate aminotransferase, nausea, decreased appetite, and vomiting. Most of these AEs were managed with supportive care or with dose reduction.
The authors concluded that nintedanib plus docetaxel combination may be an appropriate second-line treatment option for all patients with NSCLC and is particularly effective in patients with adenocarcinoma histology.
