PP217 Dynamics of disease progression during treatment with osimertinib in patients with EGFR T790M-positive non-small cell lung cancer

[摘要] Background: Despite the remarkable efficacy of osimertinib in epidermal growthfactor receptor (EGFR) T790M-positive non-small cell lung cancer (NSCLC), thedevelopment of resistance is inevitable. We aimed to analyze the disease progressionpattern during osimertinib treatment to identify potential treatment strategies.Methods: We retrospectively identified patients with advanced NSCLC who beganosimertinib treatment after progression on previous EGFR-TKI between June 2014and November 2018. Patient characteristics, efficacy outcomes, radiological sites ofmetastases, and treatment modalities before and after osimertinib were analyzed.Results: Eighty-four patients were included. On osimertinib initiation, bone (50.0%)and brain (41.9%) were the most common single metastatic sites, whereas thoracicinvolvement (73.3%) was more frequent than bone (27.4%) or brain (20.2%) metastasis during disease progression on osimertinib. Oligo-progressive disease (PD) andcentral nervous system (CNS)-sanctuary PD were observed in 15 (17.9%) and 3 (3.6%)patients, respectively. Most patients without brain metastasis (BM) at the initiation ofosimertinib administration remained BM-free (46/49, 93.9%), and 60% of patients(21/35) with pre-existing BM showed intracranial disease control despite extracranialPD. The mechanism of resistance to osimertinib was explored in 23 patients (27.4%),and T790M-loss was observed in 13 patients (56.5%); these 13 patients had worsesurvival outcomes than patients without T790M-loss (progression-free survival 6.1months vs. 13.9 months, P¼0.04, overall survival 44.9 months vs. not reached,P¼0.03).Conclusions: PD during osimertinib treatment preferentially occurred in the thoraxand pre-existing sites. Extracranial PD prevailed over intracranial PD regardless ofbaseline BM and prior brain radiation. These results support the intracranial efficacyof osimertinib and may guide treatment strategies for EGFR-mutated NSCLC with BM.

[学科分类] 社会科学、人文和艺术（综合）

[关键词] NSCLC;EGFR;Osimertinib