Real-world use of osimertinib for epidermal growth factor receptor T790M-positive non-small cell lung cancer in Japan

Objective: Adverse drug reactions (ADRs) during real-world osimertinib use were investigated in Japan. Methods: Patients with epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancer treated with second-line or later oral osimertinib per the Japanese package insert (80 mg once daily) were included. Data were collected between 28 March 2016 and 31 August 2018. Results: The median observation period in the safety analysis population (n= 3578) was 343.0 days. ADRs (defined as adverse events whose causality to osimertinib could not be denied by the attending physicians or manufacturer) were reported in 58.1% (2079/3578) of patients. ADRs of interstitial lung disease events were reported in 6.8% (245/3578; Grade >= 3, 2.9% [104/3578]) of patients, of whom 29 (11.8%) died (0.8% of patients overall). ADRs of QT interval prolonged, liver disorder and haematotoxicity were reported in 1.3% (45/3578; Grade >= 3, 0.1% [5/3578]), 5.9% (212/3578; Grade >= 3, 1.0% [35/3578]) and 11.4% (409/3578; Grade >= 3, 2.9% [104/3578]) of patients, respectively. In the efficacy analysis population (n = 3563), 119 (3.3%) patients had complete responses, 2373 (66.6%) had partial responses and 598 (16.8%) had stable disease. The objective response rate was 69.9%; disease control rate was 86.7%; and median progression-free survival (PFS) was 12.3 months. At 6 and 12 months, PFS rates were 77.4% (95% confidence interval [CI], 75.9-78.9) and 53.2% (95% CI, 51.3-55.1) and overall survival rates were 88.3% (95% CI, 87.2-89.4) and 75.4% (95% CI, 73.8-77.0), respectively. Conclusions: These data support the currently established benefit-risk assessment of osimertinib in this patient population.