A phase II study of low starting dose of afatinib as first-line treatment in patients with EGFR mutation-positive non-small-cell lung cancer (KTORG1402)

•Low-dose afatinib therapy is well tolerated with promising clinical efficacy.•The median progression-free survival is 15.2 months (95% CI: 13.2–not estimable).•The 1-year overall survival rate is 95.6% (95% CI: 89.7%–100%).•The objective response rate is 81.8% (95% CI, 81.3%–98.6%).•Adverse events of grade 3 or higher occurred in 14 patients (30.4%). Afatinib is an effective treatment in patients who have epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC), but its toxicities often require dose adjustment. Exploratory analyses of previous trials have suggested that reducing the dose of afatinib can decrease treatment-related adverse events without negatively affecting effectiveness. The aim of this study was to assess the efficacy and safety of low starting dose of afatinib with dose modification according to its toxicity in patients with EGFR mutation-positive NSCLC. This study was a multicenter, single-arm, open-label phase II trial. Treatment-naïve patients with advanced NSCLC positive for common EGFR mutations received afatinib starting in a dose of 20 mg/day. If tolerated, the dose was increased in 10-mg increments up to 50 mg/day. The primary endpoint was progression-free survival (PFS). From February 2015 through March 2016, 46 patients were enrolled. The median age was 73 years (range, 43–86), and 35 patients (72%) were women.EGFR mutation subtypes included exon 19 deletion (54%) and Leu858Arg point mutation (46%). Most patients had a performance status of 0 or 1 (91%) and a histological diagnosis of adenocarcinoma (98%). As of the data cut-off date of June 2017, the median follow-up was 18.9 months. The median PFS was 15.2 months (95% CI: 13.2–not estimable). The 1-year overall survival rate was 95.6% (95% CI: 89.7%–100%). The objective response rate was 81.8% (95% CI, 81.3%–98.6%). Adverse events of grade 3 or higher occurred in 14 patients (30.4%) and included rash/acne in 4 patients (8.7%), paronychia in 4 patients (8.7%), diarrhea in 2 patients (4.3%). There was no treatment-related death. Low starting dose of afatinib therapy showed promising clinical efficacy and good tolerability. Further investigations are warranted.