P3.02b-101 EGFR T790M Resistance Mutation in NSCLC: Real-Life Data of Austrian Patients Treated with Osimertinib: Topic: EGFR RES

Abstract

Somatic mutations in the epidermal growth factor receptor (EGFR) are detected in approximately 13% of the Austrian non-small cell lung cancer (NSCLC) patients. The EGFR T790M resistance mutation located on Exon 20 is the most common mechanism of drug resistance to EGFR tyrosine kinase inhibitors (TKI) in these patients. The mutation can be detected by re-biopsy as well liquid biopsy. Osimertinib (AZD9291), a 3rd generation EGFR-TKI, showed a highly clinical activity in these patients. We report about our experience with Osimertinib in EGFR-mutated NSCLC patients, who became resistant to first or second generation TKI's due to EGFR T790M mutation. From April 2015 to June 2016 we administered osimertinib 80 mg daily to 82 patients who had disease progression after previous treatment with an EFGR TKI. The T790M mutation status was assessed by re-biopsy and/or liquid biopsy. For liquid biopsies, blood samples were collected in EDTA-containing vacutainer tubes and processed within 2 hours after collection. Cell-free plasma DNA was extracted by using the QIAamp circulating nucleic acid kit (Qiagen) according to the manufacturer’s instructions. Mutation status was assessed with QX-100™ Droplet Digital™ PCR System (Bio-Rad). The T790M mutation status was assessed in 48 patients by liquid biopsy only and in 13 patients by re-biopsy of the tumor. In 21 patients the T790M mutation was detected by both methods. 70 (85%) patients showed a clear clinical and radiographic response. Out of these, 70 patients, 14 (17%) patients reached a complete remission, 56 (68%) patients showed partial response and in 5 (6%) patients, a stable disease after treatment with osimertinib was observed. Five patients had symptomatic brain metastasis initially without any further option of local treatment, and showed a clear a clear clinical benefit and a partial remission radiographically. Osimertinib was well tolerated. No clinically relevant significant side effects were reported. Osimertinib was highly active in our patients, while showing good safety profile. Therefore, re-biopsy or liquid biopsy should be performed in clinical routine to detect the T790M mutation. With the above described method, liquid biopsy could replace re-biopsy in clinical practice in the future.