EGFR T790M resistance mutation in NSCLC: Real-life data of patients treated with osimertinib.

e20572 Background: The EGFR T790M resistance mutation located on Exon 20 is the most common mechanism of drug resistance to EGFR tyrosine kinase inhibitors (TKI). The mutation can be detected by re-biopsy as well liquid biopsy. Osimertinib, a third 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. Methods: From April to November 2015 we administered osimertinib 80 mg daily to 30 patients who had disease progression after previous treatment with an EFGR TKI. Astra Zeneca provided osimertinib for these patients who had no further treatment options for named patient use. 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). Results: The T790M mutation status was assessed in 12 patients by liquid biopsy only and in 2 by re-biopsy of the tumor. In 16 the T790M mutation was detected by both methods. 28 (93%) showed a clear clinical and radiographic response. Out of these 7 reached a complete remission (23%), 21 showed partial response (70%). In 2 stable disease (7%) after treatment with osimertinib was observed. 4 had initial symptomatic brain metastasis, without any further option of local treatment, and showed a partial remission radiographically and a clear clinical benefit intracerebral. Osimertinib was well tolerated. No clinically relevant significant side effects were reported. Conclusions: 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.