P76.76 EGFR Tyrosine Kinase Inhibitors in Patients with Non-Small Cell Lung Cancer and the Role of Diabetes Mellitus and Metformin

Abstract

The EGFR tyrosine kinase inhibitors (TKI) had increased survival in non-small cell lung cancer (NSCLC) patients in the presence of response predictive EGFR mutations. Previously, these drugs were used in wild type patients as a 2nd line or beyond. Some laboratory studies and phase I/II trials had demonstrated a possible synergistic effect between EGFR TKI and metformin. The aim of this study is to analyze patients treated with EGFR TKI and assessing the impact of diabetes mellitus (DM) and metformin on the outcomes. A retrospective study including 75 patients with stage IV NSCLC submitted to EGFR TKI between January 2013 and December 2019. Clinicopathological characteristics were described. The progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier with Log Rank test and Cox regression, with 5% statistical significance. Thirty-one patients (n=31, 41.3%) had EGFR mutations and were treated with EGFR TKI as 1st line treatment (group 1) and 44 (58.7%) were wild type, treated with EGFR TKI in 2nd line or beyond (group 2). Twenty patients had DM and 12 patients were on metformin. The median follow-up time was 54.73 months. In group 1, the median PFS and OS were 10.37 and 18.70 months, respectively. There were no statistically significant differences in PFS and OS between patients with or without DM (p=0.28 and p=0.53), and patients treated or not with metformin (p=0.20 and p=0.50). In group 2, the median PFS and OS were 2.73 and 9.87 months, respectively. Inversely from the group 1, the median PFS was superior in patients with DM: 5.77 vs 2.63 months, HR 0.44 (95%CI 0.21-0.91), p=0.023; and in patients on metformin: 5.77 vs 2.53 months, HR 0.43 (95%CI 0.20-0.95), p=0.031. The median OS was also superior in patients with DM: 14.90 vs 7.10 months, HR 0.44 (95%CI 0.22-0.89), p=0.019. Patients that received metformin had a median OS of 12.57 months vs 7.73 months in the remaining, HR 0.47 (95%CI 0.21-1.02), p=0.051. In group 1, there were no differences in median survival among patients with DM and on metformin. However, the number of patients with DM and on metformin in this group was very small. In group 2, the median PFS and OS were superior in patients with DM, and the median PFS was superior in patients on metformin. This study has some limitations: it is retrospective, with a limited sample and it includes patients that nowadays wouldn’t be treated with EGFR TKI following the current international guidelines. Nevertheless, it will be important to study the potential association between metformin and EGFR TKI in NSCLC, regarding the fact that this drug is easily accessed in daily practice.