P1.14-47 ctDNA NGS for Guiding Crizotinib Treatment in ALK-Rearranged Advanced NSCLC Patients (Pts)

Abstract

FISH and IHC are commonly used and the golden standard for testing ALK rearrangement. However, they provide no information on fusion types or mutation status of other genes, which could be important prognostic factors. In addition, a tissue biopsy is not always applicable/preferred by pts. 43 ALK-rearranged treatment naïve advanced NSCLC pts were included. ALK-rearrangement was confirmed by ctDNA NGS with a panel of 59 tumor-related genes in 25 pts (ctDNA arm) and by IHC/FISH/tissue NGS in 18 pts (control arm). All pts received crizotinib as first-line therapy. PFS was estimated using Kaplan-Meier method and compared using log-rank test. On average, Pts in ctDNA arm were significantly older at diagnosis than pts in the control arm (56 vs. 45, p = 0.02), indicating the preferability of ctDNA NGS in elderly pts. Though older, pts in ctDNA arm had a similar mPFS with pts in the control arm (8 vs. 10 mo, p = 0.9). ALK fusion types in ctDNA arm and their associated statistics were listed in Table 1. Concomitant mutations were identified in 15 genes in 9 pathways. Frequently mutated pathways include p53 (in 8 pts) and DNA repair pathways (in 3 pts). Mutations in DNA repair pathway (5 vs. 10 mo, p = 0.06), high frequency of EML4-ALK (≥1.5%) (6 mo vs. NR, p = 0.06), and bone metastasis (6 vs. NR, p = 0.05) were associated with shorter mPFS.Table 1ALK fusion types and associated statisticssALK fusion types# of pts(Median) age at diagnosis (year)(m)PFS (mo)Average # of mutations per ptV11152101.5V3106162.8V2160-1V5'165-1V714932DCTN1-ALK147-2 Open table in a new tab Information on ALK fusion types, concomitant mutations, and mutation frequencies provided by NGS could be valuable prognostic factors and deserves further investigation. ctDNA NGS could be used as an effective alternative to identify ALK+ pts, especially for elderly pts, when tissue biopsy is inapplicable or not preferred.