Liquid Biopsy Detects Acquired Resistance Mutations Among Patients With ALK-Positive Non-Small Cell Lung Cancer Treated With Alectinib
According to preliminary results from the TANGIBLE study, liquid biopsy demonstrates high sensitivity and feasibility for detecting ALK gene alterations and resistance mechanisms among patients with ALK-rearranged non-small cell lung cancer (NSCLC) treated with first-line alectinib.
These findings were presented by Francesco Pepe, PhD, University of Naples Federico II, Napes, Italy, at the 2025 International Society of Liquid Biopsy (ISLB) Annual Meeting in Orlando, Florida.
In this study, researchers collected clinical data and plasma samples from 54 patients at the time of treatment initiation or at the time of disease progression. Cell-free DNA (cfDNA) and cfRNA were extracted from plasma samples and underwent pre-analytical evaluation for quality, quantity, and integrity. Matched tissues were assessed at relapse. Primary end points included response rate and progression-free survival (PFS).
At analysis, response rate was 65% and median PFS was 23.9 months. Disease progression occurred in 20 patients and 60% of patients underwent tissue re-biopsy. On-target acquired resistance mutations were observed in 4 patients at disease progression. An ALK I1171N pathogenic alteration occurred in 3 patients and a MET exon 14 R988C variant occurred in 1 patient in the corresponding tumor. In the remaining cases, ALK rearrangements were confirmed at relapse however no additional oncogenic driver alterations were observed.
As Dr Pepe concluded, “our molecular analyses of disease progression highlight the value of liquid biopsy as a minimally invasive tool to detect secondary acquired resistance mutations, with the potential to identify strategies to overcome resistance mechanisms.”
Source:
Pepe F. Detection and monitoring ALK gene alterations through liquid biopsy in advanced NSCLC treated with alectinib: Preliminary TANGIBLE study results. Presented at the 2025 ISLB Annual Meeting. November 1-3, 2025; Orlando, Florida. PP.38
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