A prospective, phase II trial of monotherapy with low-dose afatinib for patients with EGFR, mutation-positive, non-small cell lung cancer: Thoracic oncology research group 1632

Objectives: Afatinib is an effective treatment for patients with epidermal growth factor receptor (EGFR) mutationpositive non-small cell lung cancer (NSCLC). However, the toxicity associated with this agent often leads to dose modifications. The aim of this study was to assess the efficacy, safety and plasma concentrations of low dose afatinib monotherapy in patients with EGFR mutation-positive NSCLC. Patients and Methods: This was a multicenter, single-arm, open-label, phase II trial involving treatment-naive patients with advanced EGFR mutation-positive NSCLC. From March 2017 to September 2018, 53 patients were enrolled from 21 institutions in Japan. Patients initially received afatinib 20 mg/day orally. For patients in whom the tumor progressed within stable disease, the investigators were able to increase the afatinib dose (10 mg increments). The primary endpoint was progression-free survival (PFS). The threshold and expected median PFS was 9.2 and 13.8 months, respectively. Additionally, the correlation of the plasma concentration of low-dose afatinib with clinical outcome and adverse events were evaluated. Results: The median age of patients was 70 years (range: 37-85 years); 28 patients (52.8%) were females. The median duration of the follow-up was 20.8 months. The median PFS, and overall survival were 12.6 months (90% confidence interval [CI]: 9.7-14.3 months), and not reached, respectively. The primary endpoint was met. The objective response rate and disease control rate were 66.0% (95% CI: 51.7-78.5) and 92.5% (95% CI: 81.8-97.9), respectively. Grade >= 3 adverse events occurred in 12 patients (22.6%), including diarrhea in four patients (7.5%). The rate of adverse events was lower than that observed in previous phase III studies of 40 mg afatinib. Conclusion: Based on its promising clinical efficacy and tolerability profile, monotherapy with low-dose afatinib should become one of the standard therapies for EGFR mutation-positive NSCLC.