P2.01-71 Comprehensive Analysis of EGFR T790M-Mutant Abundance of Different Technologies and Its Effect on Efficacy of Osimertinib in Advanced NSCLC

Abstract

Osimertinib has been adopted as the standard of care for T790M-mediated acquired epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance. And detecting EGFR T790M mutation can be challenging in routine care, low abundance of the mutation and difficulty for re-biopsy in patients with advanced disease. We aim to compare droplet digital PCR (ddPCR) and next generation sequencing (NGS) in T790M mutation testing, and analyze whether the abundance of T790M mutation is associated with the efficacy of osimertinib in advanced Non–small cell lung cancer (NSCLC). We retrospectively studied 132 T790M-positive advanced NSCLC patients who have received osimertinib after acquired TKI resistance from April 2017 to August 2018 at our institution. Treatment response was evaluated and survival data were collected and analyzed. Among the 132 patients, 18(13.6%) had adopted amplifcation refractory mutation system (ARMS), 58(43.9%) adopted ddPCR, 43(32.6%) used NGS in T790M testing, and the detection methods of 13(9.9%) patients were unknown. Data of T790M-mutatnt abundance were obtained in 64 patients, 57 of whom were tested by ddPCR in plasma and the other 7 by NGS. The median progression free survival (PFS) was 15 months, median OS was not reached, objective response rate (ORR) was 88%. We found that ARMS, ddPCR, NGS have no difference in T790M testing (p=0.114). Among the 57 ddPCR testing patients with the abundance of T790M, there was no difference in PFS of T790M abundance in the cutoff value of 0.5 (p=0.303). Our results suggest that ARMS, ddPCR and NGS are all useful and reliable methods in EGFR T790M mutation detection. And the association between the abundance of T790M mutation using ddPCR in plasma and the efficacy of osimertinib seemed not strong and remained to be explored.