P76.52 Liquid Biopsy and PET Parameters as Predictive Factors of Osimertinib Treatment in Advanced EGFR-Mutated NSCLC

Abstract

Osimertinib resistance constitutes a major challenge for the management of advanced EGFR-mutated (adv-EGFR+) NSCLC and the identification of predictive factors is largely needed. We aimed to investigate a putative role of liquid biopsy (LB) and metabolic parameters in predicting response to osimertinib. We prospectively enrolled adv-EGFR+ NSCLC patients (pts) who were treated with osimertinib both in first- (1L) and second-line (2L). Pts underwent LB before starting of osimertinib and EGFR activating mutation (EGFRact) allele frequency (AF) was assessed on circulating free DNA (cfDNA) by ddPCR. Pts with EGFRact AF > 0 were defined as shedders. FDG-PET was performed at baseline and after 1 month of treatment; metabolic response (MR) was assessed as per PERCIST 1.0 criteria. Tumor response was assessed by CT-scan after 2-3 months (mos) as per RECIST 1.1 criteria. FDG-PET parameters (maximum standardized uptake value [SUVmax], SUVpeak, lean body mass corrected SUV [SULpeak], total lesion glycolysis [TLG]) cut-offs were calculated using ROC curve analysis. 23 pts with adv-EGFR+ NSCLC (1L=15; 2L=8) were enrolled at the time of data cut-off (April 21th, 2020). Overall, mPFS was 7.1 mos (95% CI, 0.3-13.9) and mOS was not reached (Range, 1.1-17.9). Basal shedders had a significantly shorter mPFS compared to non-shedders (mPFS: 3.6 vs 17.0 mos, p<0.05). Among all FDG-PET parameters, basal TLG (bTLG) was significantly related to basal EGFRact AF (Spearman r: 0.57, 95%CI 0.17-0.81, p<0.05). Pts who had a high bTLG had a significantly shorter mPFS vs pts with a low bTLG (mPFS: 3.6 vs 14.2 mos, p<0.05). Pts who had a high bTLG and were shedders had a significantly shorter mPFS vs pts who had only 1 of the 2 features and who had none (mPFS: 3.0 vs 7.1 vs 17.0 mos, respectively, p<0.05). Among basal shedders (n=11), the clearance of EGFRact after 1 month was significantly associated with MR (p<0.05). Pts who achieved a MR at the 1-month FDG-PET had a significantly longer mPFS vs pts who did not (mPFS: 14.2 vs 5.5 mos, p<0.05). EGFRact shedding and high bTLG identified a poor responder group to osimertinib. Integration of basal and early cfDNA analysis and metabolic parameters might be a promising not-invasive approach to predict benefit to osimertinib.