639P - Serial ctDNA profiling as a catalyst for tailored therapeutics in advanced cancer: Analysis of two precision medicine studies

Background

Circulating tumor DNA (ctDNA) analysis has become a pivotal component of modern oncology, offering a minimally invasive method for molecular profiling of tumors. While a single ctDNA profiling session can provide essential insights for treatment tailoring, the full impact of serial profiling on guiding therapeutic decisions in patients with advanced cancers has not been explored.

Methods

This study analyzed adult patients with advanced solid tumors enrolled in the BIP (NCT02534649) and STING (NCT04932525) trials between 04/2021 and 12/2023, who underwent sequential liquid biopsies during their therapeutic journey. ctDNA profiling was done by using the FDA/CE-IVD label-approved FoundationOne 324-gene panel, and molecular alterations were categorized as per the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT).

Results

A total of 586 patients (327 men, 259 women) were enrolled, with a median age of 61 years (range: 22-91). The most common primary tumors included NSCLC (31.7%), colorectal (15.9%), and prostate cancer (10.2%). The median number of liquid biopsies performed per patient was 2, ranging from 2 to 17. The initial liquid biopsy (LB) revealed actionable molecular alterations in 366 patients (62.5%, ESCAT I: n=173 [29.5%]). Subsequent LB brought to light new actionable ESCAT molecular alterations in 210 (38%) of patients, and 126 (21.5%) demonstrated improved ESCAT scores over time. Additionally, resistance mechanisms were identified in subsequent biopsies for 140 patients (23.9%). The initial liquid biopsy (LB) enabled the molecular tumor board (MTB) to provide specific therapeutic recommendations for 195 patients (33.3%), while subsequent LBs led to MTB recommendations for 221 patients (37.7%).

Conclusions

This study represents the first comprehensive investigation into the utility of repeated ctDNA profiling using a comprehensive genomic profiling panel in patients with advanced cancers. Serial ctDNA profiling significantly enhances the management of advanced cancers by enabling real-time adjustments to treatment based on evolving tumor genomic information.

Clinical trial identification

NCT02534649; NCT04932525.

Editorial acknowledgement

Legal entity responsible for the study

A. Italiano.

Funding

Has not received any funding.

Disclosure

S. Cousin: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, Lilly, Roche; Non-Financial Interests, Principal Investigator: AstraZeneca, Daiichi, Gilead, Takeda, Sanofi, MSD, GSK, BMS. A. Bayle: Financial Interests, Personal, Advisory Board, ASCO 2022 & ESMO 2023: Sanofi; Financial Interests, Personal, Invited Speaker, Health Economics conference: Roche; Financial Interests, Personal, Other, Expert at the Commission for the Evaluation of Diagnostic, Prognostic and Predictive Health Technologies: HAS (French National Authority for Health); Other, Transportation and accommodation support for the ASCO 2023 Congress: Pfizer. L. Blouin: Other, Unfunded public speaking (JEPO conference): AstraZeneca. I. Soubeyran: Financial Interests, Institutional, Invited Speaker, congress, meeting: AstraZeneca; Financial Interests, Institutional, Funding, research funding: AstraZeneca. A. Hollebecque: Financial Interests, Personal, Invited Speaker: Servier, Incyte, Eisai; Financial Interests, Personal, Advisory Board: Basilea, Taiho, Relay Therapeutics, QED Therapeutics, Debiopharm, MSD, Boehringer Ingelheim; Financial Interests, Institutional, Funding: Incyte; Financial Interests, Institutional, Research Grant: AstraZeneca; Non-Financial Interests, Principal Investigator, M19-345: AbbVie; Non-Financial Interests, Principal Investigator, CO42216, WP42627, CO40939: Roche; Non-Financial Interests, Principal Investigator, MCLA-158: Merus; Non-Financial Interests, Principal Investigator, SGNB6A: Seatle Genetics; Non-Financial Interests, Principal Investigator, TAS-120-202: Taiho; Non-Financial Interests, Principal Investigator, Krystal-10: Mirati; Non-Financial Interests, Principal Investigator, ADP-0033: Adaptimmune; Non-Financial Interests, Principal Investigator, ACT16902: Sanofi; Non-Financial Interests, Principal Investigator, C4201002: Pfizer; Non-Financial Interests, Principal Investigator, RLY-4008: Relay Therapeutics; Non-Financial Interests, Principal Investigator, CC-90011: Celgene/BMS; Non-Financial Interests, Principal Investigator, Loxo-IDH: Loxo/Lilly; Non-Financial Interests, Principal Investigator: AstraZeneca; Non-Financial Interests, Principal Investigator, SN-201 study: Sotio; Non-Financial Interests, Principal Investigator, Tropics-03: Gilead; Non-Financial Interests, Principal Investigator, BI1403: Boehringer Ingelheim. Y. Loriot: Financial Interests, Personal, Advisory Board: Merck Kga, Pfizer, Gilead, Seattle Genetics, Taiho; Financial Interests, Personal, Other, lectures, advisory boards: MSD, AstraZeneca, Astellas, Janssen, Roche, BMS; Financial Interests, Institutional, Research Grant: Janssen, Sanofi, MSD, Roche, Celsius; Financial Interests, Institutional, Steering Committee Member: Janssen; Financial Interests, Steering Committee Member: MSD, Astellas, Gilead/Immunomedics, Taiho; Financial Interests, Personal, Steering Committee Member: Basilea; Financial Interests, Institutional, Local PI: Pfizer, MSD, Janssen, Exelixis, AstraZeneca, Pfizer, Merck Kga, BMS, Astellas, Gilead, Incyte; Financial Interests, Institutional, Coordinating PI: Janssen; Non-Financial Interests, Member: ESMO, ASCO, AACR; Non-Financial Interests, Other, scientific committee: ARC. B. Besse: Financial Interests, Institutional, Advisory Board: Amgen, AstraZeneca, BeiGene, Blueprint Medicine, Cergentis, Chugai Pharmaceutical, Daiichi Sankyo, F. Hoffmann-La Roche, Inivata, Pfizer, PharmaMar, Sanofi Aventis, Springer Healthcare Ltd, 4D Pharma, AbbVie, Da Voltera, Eli Lilly, Ellipse pharma Ltd, F-Star, GSK, Janssen, Onxeo, Ose Immunotherapeutics, Socar Research, Taiho Oncology, Turning Point Therapeutics; Financial Interests, Institutional, Invited Speaker: Genzyme Corporation, Hedera Dx, Medscape, MSD; Financial Interests, Institutional, Local PI: AbbVie, Amgen, Blueprint Medicines, Daiichi Sankyo, Pfizer, Roche-Genentech, Turning Point Therapeutics, Nuvalent, Enliven, Prelude Therapeutics; Financial Interests, Institutional, Coordinating PI: AstraZeneca, OSE Immunotherapeutics, Sanofi, Taiho; Financial Interests, Institutional, Steering Committee Member: BeiGene, GSK, Janssen, Takeda, Genmab; Financial Interests, Institutional, Funding: Cristal Therapeutics. J. Soria: Financial Interests, Personal, Full or part-time Employment, From Sept 2017 to Dec 2019: AstraZeneca; Financial Interests, Personal, Member of Board of Directors, 2019-2021: Hookipa Pharmaceuticals; Financial Interests, Personal, Full or part-time Employment, SVP Amgen since August 2021: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. F. Barlesi: Financial Interests, Institutional, Advisory Board: AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann-La Roche Ltd, Novartis, Merck, Mirati, MSD, Pierre Fabre, Pfizer, Sanofi Aventis, Seattle Genetics, Takeda, AbbVie, ACEA, Amgen, Eisai, Ignyta; Non-Financial Interests, Principal Investigator: AstraZeneca, BMS, Merck, Pierre Fabre, F. Hoffmann-La Roche Ltd., Innate Pharma, Mirati. F. André: Financial Interests, Personal, Advisory Board: Lilly France; Financial Interests, Institutional, Advisory Board: AstraZeneca, Daiichi Sankyo, Roche, Lilly, Pfizer, Owkin, Novartis, Guardant Health, N-Power Medicine, Servier, Gilead, Boston Pharmaceuticals; Financial Interests, Institutional, Research Grant: AstraZeneca, Lilly, Novartis, Pfizer, Roche, Daiichi, Guardant Health, Owkin. C.P. Massard: Consultant/Advisory fees: Amgen, Astellas, AstraZeneca, Bayer Ipsen, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, Netcancer, PegascyPrincipal/sub-Investigator of Clinical Trials for AbbVie, Aduro, Agios, Amgen, Argenx, Astex, AstraZeneca, Aveo Pharmaceuticals, Bayer, BeiGene, Blueprint, BMS, Boeringer Ingelheim, Celgene, Chugai, Clovis, Daiichi Sankyo, Debiopharm, Eisai, Eos, Exelixis, Forma, Gamamabs, Genentech, Gortec, GSK, H3 Biomedecine, Incyte, Innate Pharma, Janssen, Kura Oncology, Kyowa, Lilly, Loxo, Lysarc, Lytix Biopharma, Medimmune, Menarini, Merus, MSD, Nanobiotix, Nektar Therapeutics, Novartis, Octimet, Oncoethix, Oncopeptides AB, Orion, Pfizer, PharmaMar, Pierre Fabre, Roche, Sanofi, Servier, Sierra Oncology, Taiho, Takeda, Tesaro, Xencor. A. Italiano: Financial Interests, Personal, Advisory Board: Bayer, Roche, Philips, Chugai, GSK; Financial Interests, Institutional, Coordinating PI: Bayer, AstraZeneca, Roche, MSD, Ipsen, Merck. All other authors have declared no conflicts of interest.