Impact of epidermal growth factor receptor mutation on clinical outcomes of nintedanib plus docetaxel in patients with previously treated non-small cell lung cancer from the Korean named patient program

Objectives: Anti-angiogenic agents are reported to exert clinical activity on epidermal growth factor receptor (EGFR) mutant non-small-cell lung cancers. We evaluated the clinical outcomes of nintedanib and docetaxel in refractory NSCLC according to EGFR mutation status during the Korean nintedanib named patient program. Methods: Docetaxel was administered either 75 or 37.5 mg/m² on D1, D8 q every 3 weeks for 4-6 cycles plus nintedanib 200 mg orally twice daily until disease progression or unacceptable toxicity. Results: Sixty-two patients were enrolled for study. Twenty-eight patients with activating EGFR mutations progressed after EGFR-tyrosine kinase inhibitors (TKI) therapy and 25 out of 28 patients showing progression after platinum doublet chemotherapy were enrolled. The objective response rate was 29% and median PFS and OS were 3.9 months and 11.7 months. Based on the EGFR mutation status, the objective response rate was 39.3 vs. 21.9% (EGFR mut(+) vs. EGFR mut(-), p = 0.142) and median PFS was 6.5 vs. 3.3 months (EGFR mut(+) vs. EGFR mut(-), p = 0.009). No treatment-related deaths were reported. The most frequent drug-related adverse events (AE) were neutropenia (53.2%) and diarrhea (37.1%). Treatment in 12 patients (19.3%) was permanently discontinued due to AEs without disease progression. Conclusions: Our data indicated that nintedanib-docetaxel combination could be considered to be effective treatment in EGFR TKI-resistant EGFR mutant NSCLC.