P3.02b-015 Impact of Metastatic Status on the Prognosis of Patients Treated with First Generation EGFR-TKIs: Topic: EGFR Biomarkers

Abstract

First generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) such as gefitinib (GEF) or erlotinib (ERL) are effective for patients harboring EGFR mutations positive non-small cell lung cancer (NSCLC). To know the impact of metastatic status on patients treated with EGFR-TKIs is important. The objective of this study is to know the impact of metastatic status including brain metastasis, bone metastasis, liver metastasis and pleural effusion on the prognosis of patients treated with first generation EGFR-TKIs. The pathology files of National Hospital Organization Kinki-chuo Chest Medical Center from 2009 to 2014 were retrospectively reviewed and 533 patients were EGFR mutation positive NSCLC. Patients with stage IA to IIIA and small cell lung cancer were excluded. From 299 stage IIIB, IV and relapsed NSCLC patients, 178 patients treated with GEF or ERL as first line treatment were enrolled for the study. Metastatic status, progression free survival (PFS), overall survival (OS) and response rate (RR) were investigated. We also evaluated the relationship between the number of metastatic organs and prognosis. Fifty-one patients were male and median age at the time of first line treatment was 72 years (range 39-91). Number of patients with adenocarcinoma was 168 and 156 patients were treated with GEF. In log-rank test, PFS and OS were significantly worse in patients with brain metastasis (8.0m vs 13.2m, p= 0.008; 20.2m vs 38.0m, p< 0.001 respectively), bone metastasis (8.8m vs 15.4m, p< 0.001; 24.0m vs 32.1m, p= 0.020 respectively), liver metastasis (6.7m vs 12.5m, p< 0.001; 13.4m vs 32.1m, p< 0.001 respectively) and pleural effusion (10.8m vs 12.2m, p= 0.033; 21.9m vs 34.9m, p= 0.004 respectively) at the time of first line treatment compared with patients without each metastasis. In cox proportional hazards models multivariate analysis, bone metastasis had correlated with worse PFS (HR 2.110, 95% CI 1.437-3.093, p< 0.001) and moreover, brain metastasis had correlated with worse OS (HR 2.414, 95%CI 1.464-3.951, p< 0.001). There were no relationships between metastatic status and RR. Furthermore, the much number of metastasized organs (no metastasis, 1 metastasis and 2 or more metastasis) was significantly related to worse PFS (19.3m vs 12.5m vs 6.6m, p< 0.001) and OS (46.1m vs 29.9m vs 15.1m, p< 0.001). Bone metastasis had correlated with worse PFS and brain metastasis had correlated with worse OS in patients treated with first generation EGFR-TKIs. Moreover, the much number of metastasized organs was related to worse PFS and OS.