151P - Unravelling the limitations of next-generation sequencing (NGS)-based liquid biopsy (LB) across solid tumors: The PREICO-LB project

Background

NGS-LB allows high-throughput ctDNA analysis with the advantage of not requiring tumor tissue for molecular profiling. However, several factors such as assay sensitivity, tumor characteristics and response to treatment can impact ctDNA concentrations, thus limiting the LB utility. This study aims to describe the experience gained with LB at the Catalan Institute of Oncology (ICO) network in Spain.

Methods

Multicentric retrospective study of adult patients (pt) with multiple solid tumors evaluated through the molecular PRE-screening program at ICO (PREICO). LB was considered in case of no available formalin fixed paraffin embedded tissue sample (FFPE) for NGS analysis or pt with progressive disease not amenable for re-biopsy. Each LB consisted of two 8.5 ml cfDNA collection tube extraction and was analyzed with AVENIO® expanded kit, an NGS-LB research assay with 77 genes. Molecular results were reviewed in dedicated LB molecular tumor boards.

Results

From May22 to Dec23, 63 pt were included. Most common tumors were NSCLC (24%), colon (17%), pancreatic-biliary (17%), esophagogastric (11%) and hepatocarcinoma (HCC 10%), with a pooled miscellany group of 21% pt. Only 16% pt had actionable findings for matched targeted therapy. Of note, 29% pt harbored some molecular aberrations considered not actionable nowadays, of whom 6/18 mutations (mut) were in the MAPK pathway: 3 KRASmut non-G12C, 2 BRAFmut non-V600E and 1 NRASmut. No alterations were detected in 55% pt, though 10 pt had tumor types with usually low frequency of aberrations such as 5 HCC, 2 mesothelioma, 1 neuroendocrine, 1 SCCHN, and 1 non-melanoma skin cancer. No emergent resistance mechanisms to anti-EGFR therapy were detected in 8 colon pt, and LB was unable to detect KRASmut Q61P/G13D previously detected in FFPE NGS of 2 colon cancer pt.

Conclusions

Our exploratory study suggests that results from pan-cancer NGS-LB analysis should be taken with caution since customized gene panels could be unable to detect any alterations in LB for most pt (55%). Future improvements in gene panel coverage, selection of best candidates and definition of optimal extraction timepoints, will help in delineating a successful LB development.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Catalan Institute of Oncology.

Funding

Has not received any funding.

Disclosure

C. Hierro: Financial Interests, Personal, Invited Speaker: MSD, Lilly, AstraZeneca; Financial Interests, Personal, Research Grant, Principal Investigator of Merck Research Grant in Personalized Medicine 2020: Merck; Non-Financial Interests, Personal, Principal Investigator, Clinical Trial: BMS, Jazz Therapeutics, ALX Oncology, AstraZeneca, MSD; Other, Personal, Other, Travel fees: BMS, Amgen, Roche, Merck. P. Sàbat Viltró: Other, Personal, Other, Training: Lilly. J.J. Soto Castillo: Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer, Eisai, MSD, Seagen. M. Calvo: Financial Interests, Personal, Advisory Board: Roche, Eisai; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca; Financial Interests, Personal, Other, Safety. Phase I trial: Nerviano. M. Oliva Bernal: Financial Interests, Personal, Invited Speaker: Merck, MSD, BMS, MSD; Financial Interests, Personal, Advisory Board: Merck, MSD; Financial Interests, Personal, Invited Speaker, Teaching activities: MSD, Merck; Financial Interests, Personal, Other, IDMC: Transgene; Financial Interests, Personal and Institutional, Funding: Roche; Financial Interests, Institutional, Invited Speaker: ALX Oncology, MSD, ISA Therapeutics BV, Roche, Ayala Therapeutics, AbbVie, Bayer, Boehringer Ingelheim, Merck, Debiopharm, Seagen, Gilead, Beigene, Nykode; Financial Interests, Institutional, Funding: GSK; Non-Financial Interests, Institutional, Product Samples: Roche. J.C. Ruffinelli Rodriguez: Financial Interests, Personal, Invited Speaker: Amgen; Other, Personal, Other, Travel and Accommodation: MSD, Merck, Advanced Accelerator Applications, Esteve. E. Carcereny: Financial Interests, Personal, Invited Speaker: Takeda, MSD, AstraZeneca; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Research Grant: Merk. C. Fina Planas: Financial Interests, Personal, Invited Speaker: BMS, Ipsen; Non-Financial Interests, Personal, Principal Investigator: Janssen. M. Gil Martín: Financial Interests, Personal, Invited Speaker: MSD, GSK, Clovis; Financial Interests, Personal, Advisory Board: AstraZeneca. E. Nadal: Financial Interests, Personal, Advisory Board: Roche, Bristol Myers Squibb, Merck Sharp & Dohme, Boehringer Ingelheim, Lilly, Pfizer, Merck Serono, Daiichi Sankyo, AstraZeneca, Takeda, Amgen, Sanofi, Qiagen, Janssen, Regeneron, Pierre Fabre; Financial Interests, Personal, Invited Speaker: Roche, Bristol Myers Squibb, Merck Sharp & Dohme, Lilly, Pfizer, Sanofi, AstraZeneca, Takeda, Amgen, Qiagen, Janssen, Daiichi Sankyo, Illumina; Financial Interests, Personal and Institutional, Funding, Clinical trial funded by Roche: Roche; Financial Interests, Personal and Institutional, Funding, Merck Serono funded a clinical trial: Merck Serono; Financial Interests, Personal and Institutional, Funding, BMS funded a clinical trial: Bristol Myers Squibb; Non-Financial Interests, Personal, Advisory Role: Pfizer, Roche, Apollomics, Transgene; Other, Personal, Other, Member of the Steering Committee: Spanish Lung Cancer Group (GECP). J. Martin-Liberal: Financial Interests, Personal, Invited Speaker: Astellas, Bristol Myers Squibb, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Sanofi; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Novartis, Pierre Fabre, Roche, Sanofi, Highlight Therapeutics; Financial Interests, Personal, Other, Travel grant: Bristol Myers Squibb, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Ipsen, Merck. All other authors have declared no conflicts of interest.