P3.02b-077 Osimertinib Expanded Access Program for Previously Treated Patients With Advanced EGFR T790M Mutation-Positive NSCLC: Topic: EGFR Clinical

Abstract

The US AZD9291 Expanded Access Program (EAP) was conducted to provide compassionate access to osimertinib for previously treated patients with advanced/metastatic, epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC). Patients (≥18 years old) with EGFR T790M mutation-positive NSCLC and a WHO Performance Status of 0–2 who had received ≥1 prior lines of therapy that included an EGFR tyrosine kinase inhibitor (TKI) or progressed during EGFR TKI treatment, were eligible. Patients received osimertinib at 80mg oral, once-daily, until dose reduction, discontinuation or EAP completion following FDA approval (November 2015). Patient demographics, T790M testing, safety and tolerability including serious adverse events (SAEs) were collected. Patient response was collected at investigator discretion, but not mandated by the EAP protocol. For required T790M diagnostics, various testing methods were permitted. Osimertinib was provided to 248 EGFR T790M mutation-positive patients through the EAP (May 2015 to November 2015). Of the 244 patients with reported T790M method data, the majority were enrolled based on samples from tissue (n=187) and blood (n=48), whereas others were based on pleural fluid (n=5) or urine (n=4). Use of noninvasive (ie, liquid biopsy) T790M testing varied across the 25 participating sites: 5 sites (20%) enrolled no patients using liquid biopsy, 2 (8%) enrolled all patients based on liquid biopsy, and 18 (72%) enrolled based on different methods. Median age was 65 years old (range, 31–91), 69% of patients were female, and 85% of patients received ≥2 prior cancer treatments. Prior erlotinib therapy was reported in 96% of patients. Starting daily dose of 80mg osimertinib was maintained throughout the study in 238 patients (96%) and reduced to 40mg in 10 patients because of AEs/intolerance. Once commercially available, most patients (n=205; 83%) continued on osimertinib, thus completing the EAP. Reasons for EAP withdrawal prior to conversion included disease progression (7%) or death (5%). A total of 19 (8%) deaths were reported during the EAP, mostly attributed to lung cancer/disease progression and/or respiratory complications (n=16; 84%). Five (2%) patients reported drug-related SAEs, including dyspnea, deep vein thrombosis, femur fracture, increased alanine aminotransferase, and pneumonitis. In a real-world setting, US AZD9291 EAP demonstrated that osimertinib was well tolerated in previously treated patients with EGFR T790M mutation-positive NSCLC, and most converted to commercial therapy following FDA approval. This EAP suggests early uptake of non-invasive T790M testing at some centers.