The aim of this study was to assess the efficacy and safety of afatinib, an epidermal growth factor receptor (EGFR) tyrosin kinase inhibitor (TKI), for elderly Japanese patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC).
NEJ027 was single-arm, multicenter, open-label phase II study of first-line afatinib monotherapy. Patients aged 75 or older with stage IIIB/IV or recurrent non-squamous NSCLC harboring EGFR mutations were enrolled. The patients received afatinib at a start dose of 40mg/day until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR), and the secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety profile.
Between January 28, 2016, and September 14, 2017, a total of 38 patients with a median age of 77 years (range, 75-91) were enrolled (15 males; 21 Eastern Cooperative Oncology Group performance status 0; all adenocarcinoma; 23 EGFR exon 19 deletion mutation) in safety analysis and 37 in the full analysis set. The ORR was 75.7% (95% confidence interval: CI 61.9-89.5) and DCR was 89.2%. The median PFS was 14.3 months (95% CI 9.9-not reached). The common grade 3 or 4 adverse events were diarrhea (10 [26.3%]), stomatitis (5 [13.2%]), rash (2 [5.3%]), appetite loss (5 [13.2%]), nail abnormality (4 [10.5%]) and pneumonitis (2 [5.3%]). 30 patients (78.9%) required 1 step or more dose reduction.
Although the percentage of patients requiring dose reduction seemed relatively higher than that in previous studies, first-line afatinib at a start dose of 40mg/day was found to be well-tolerated by dose adjustment and effective in elderly patients with advanced non-squamous NSCLC harboring EGFR mutations.
Clinical trial identification
Legal entity responsible for the study
North East Japan Study Group.
Japan Agency for Medical Research and Development.
O. Yamaguchi: Honoraria: Bristol-Myers Squibb, Ono Pharm and AstraZeneca. S. Watanabe: Grants: Boehringer Ingelheim, during the conduct of the study; Grants and personal fees: Boehringer Ingelheim, personal fees: Chugai Pharma, Ono Pharmaceutical, Lilly, AstraZeneca, Taiho Pharmaceutical, Pfizer, Bristol-Myers Squibb and Novartis Pharma. M. Mori: Lecture fees: Boehringer Ingelheim. O. Hataji: Lecture fees: Novartis, Boehringer Ingelheim; Research fundings: Novartis, Boehringer Ingelheim, Kyorin Pharm, Bayer Health Care, Daiichi Sankyo, Glaxo Smith Kline. S. Morita: Corporate-sponsored research: Boehringer Ingelheim; Honorarium: Boehringer Ingelheim. K. Kobayashi: Advisory board: AstraZeneca. A. Gemma: Lecture fee: Boehringer Ingelheim. All other authors have declared no conflicts of interest.