Abstract
INTRODUCTION: The osimertinib (AZD9291) US Expanded Access Program (EAP) provided compassionate access to osimertinib prior to US Food and Drug Administration (FDA) approval for patients with advanced/metastatic epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancer (NSCLC) following progression on tyrosine kinase inhibitors (TKIs) targeting EGFR. Here, we report the patient demographics, safety and tolerability, and diagnostic methods used for T790M testing in the EAP. METHODS: Adult patients with EGFR T790M-positive NSCLC following progression on prior EGFR-TKI therapy (irrespective of line of therapy) were enrolled in the EAP and treated with 80 mg osimertinib once daily until dose reduction, discontinuation, or completion of the EAP following FDA approval (November 2015). Various testing methods were allowed for the required T790M testing. RESULTS: In total, 248 patients from 25 centers throughout the USA were enrolled in the EAP. The starting dose of 80 mg osimertinib once daily was maintained for 96% (n = 238) of patients over the duration of the EAP (median duration of exposure 84 days). Most patients (overall 83% [n = 205/238]; patients aged ≥ 75 years 83% [n = 48/58]) completed the EAP and transitioned to commercially available osimertinib following FDA approval. Serious adverse events considered to be treatment related by investigators were reported in five patients (2%), all aged ≥ 65 years, and were dyspnea, deep vein thrombosis, femur fracture, alanine aminotransferase increase, and pneumonitis, respectively. A variety of biospecimen types were collected: solid tumor tissue (73%), blood (20%), cytology (6%), and urine (2%). PCR-based methods were most commonly used for determining EGFR mutation status (47%) followed by next-generation sequencing (33%). CONCLUSION: In a real-world setting, osimertinib was well tolerated, and most patients, including patients aged ≥ 75 years, transitioned to commercially available osimertinib following FDA approval. The EAP suggests there has been an uptake of minimally invasive T790M testing methods at some centers. FUNDING: AstraZeneca (Wilmington, DE, USA).