Abstract 1284P
Background
Liquid biopsies (LB) are a non-invasive source of tumor molecular information. Here, we evaluate the clinical utility of LB for the management of ALK-positive non-small cell lung cancer (NSCLC) patients using RNA from platelets and extracellular vesicles (EVs), and circulating tumor DNA (ctDNA).
Methods
Blood and tissue samples were collected from 30 ALK-positive, stage IIIB-IV NSCLC patients prior to initiating first-line brigatinib treatment. Nucleic acids from formalin-fixed-paraffin embedded (FFPE) tissue and plasma samples were analyzed by next-generation sequencing (NGS) using the Oncomine Focus Assay or the TruSight Oncology 500 ctDNA panel, respectively. EVs and platelets were isolated from plasma samples by differential centrifugation and RNA within these compartments was evaluated by QuantStudio 3D Digital PCR System and, when possible, by nCounter.
Results
The overall response rate was 93% (95%CI: 75.1, 98.4). Patients were followed for a median of 33.6 months. Median duration of response was 14.7 months. The median progression-free survival (PFS) was 33.8 months (6.2 – NR months) and median overall survival (OS) was not reached (NR). NGS analysis of FFPE samples enabled the detection of ALK fusion variants in all samples. Eleven patients harbored EML4-ALK variant 1 (v1), 5 carried v2, and 7 harbored the V3 and 7 had other variants or a combination of more than one variant. There were no significant differences in survival outcomes according to the type of variant. LB analysis revealed fusion detection rates of 33% using EVs, 17% in platelets, and 71% by ctDNA NGS profiling. Additionally, ctDNA provided information about tumor mutational burden (TMB) and ctDNA levels. Patients with blood TMB below 80 mutation/Mb exhibited significantly improved outcomes in terms of progression-free survival (PFS) (HR= 0.11; 95%CI: 0.02-0.76). Similarly, those with low baseline ctDNA levels (Maximum VAF ≤1%) demonstrated significantly superior PFS (HR= 0.11; 95%CI: 0.02-0.61) and overall survival (OS) (HR= 0.14; 95%CI: 0.03-0.82) compared to counterparts with higher ctDNA levels.
Conclusions
Detection rate by ctDNA profiling is higher compared with RNA-based approaches and it is of prognostic significance.
Clinical trial identification
NCT04223596.
Editorial acknowledgement
Legal entity responsible for the study
Fundacion GECP/Spanish Lung Cancer Group.
Funding
Takeda.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
1260P - Efficacy and safety of sunvozertinib in prior platinum treated NSCLC patients with EGFR exon 20 insertion mutations: Primary analysis from the multinational WU-KONG1B pivotal study
Presenter: Ludovic Doucet
Session: Poster session 05
1261P - Efficacy of glecirasib in combination with JAB-3312 as a front-line treatment for patients with KRAS p.G12C mutated NSCLC with PD-L1 expression levels or co-mutations
Presenter: Jie Wang
Session: Poster session 05
1262P - Combined molecular analysis of circulating tumour DNA and tumour tissue to identify osimertinib resistance
Presenter: Tijmen van der Wel
Session: Poster session 05
1263P - Biomarker analysis of plasma samples in YAMATO study: A randomized phase II trial comparing switching treatment of osimertinib following 8 months of afatinib (A) and osimertinib alone (B) in untreated advanced NSCLC patients with common EGFR mutation (TORG1939/WJOG12919L)
Presenter: Hiroshige Yoshioka
Session: Poster session 05
1264P - Real-world evidence of treatment practices and therapeutic outcomes for newly diagnosed NSCLC patients with non-classical EGFR mutations demonstrates high unmet medical need
Presenter: John Heymach
Session: Poster session 05
1265P - A promising MET-EGFR bispecific nanobody-drug conjugate therapy for multiple solid tumours
Presenter: xianghai Cai
Session: Poster session 05
1266P - Interim analysis from the multicenter ROSE study: Radiation during osimertinib treatment safety and efficacy cohort
Presenter: Amanda Tufman
Session: Poster session 05
1267P - Sequential afatinib (AFA) to osimertinib (OSI) in EGFR-mutant NSCLC: Primary analysis of Gio-Tag Japan, a multicenter prospective observational study
Presenter: Naoto Takase
Session: Poster session 05
1268P - Concordances assessment between MET-positive circulating tumour cells and disease progression in patients with EGFR mutated NSCLC
Presenter: Jieun Park
Session: Poster session 05
1269P - Preventing infusion-related reactions with intravenous amivantamab: Updated results from SKIPPirr, a phase II study
Presenter: Luis Paz-Ares
Session: Poster session 05