125P - Circulating tumour DNA (ctDNA) as a prognostic biomarker in patients (pts) with refractory metastatic colorectal cancer (mCRC) receiving TAS102 with or without bevacizumab

Background

The SUNLIGHT trial revealed improved survival with TAS102/Bevacizumab (TASBev) over TAS102 (TAS) in refractory mCRC pts, highlighting the importance of antiangiogenic therapy in this setting. We explore the role of baseline ctDNA as a biomarker in mCRC pts receiving TAS or TASBev.

Methods

We collected data from mCRC pts who received TAS/TASBev ≥3^rd line and who had evaluable ctDNA samples at baseline (before starting TAS/TASBev) using the ctDNA NGS test (Guardant) in our center. Driver genes were selected based on the highest mutant allele fraction (plMAF) when ≥2 driver genes were detected within the same sample. We explored OS and PFS based on plMAF levels using Kaplan-Meier method. Multivariable Cox analysis was conducted, including the presence of liver disease, Bev treatment, and plMAF.

Results

32 refractory mCRC pts were included, 14 (44%) received TASBev and 18 (56%) TAS. 12 pts were RASwt (38%). Pts were stratified as high (≥ 15.5%) (14 pts; 44%) or low (< 15.5%) (18 pts; 56%) plMAF (based on better cut-off for OS). Median MAF was 9.1 (IQR: 0.53-24.4); being lower in pts treated with TAS (3.6) vs TASBev (12.6). Higher OS was reached in those pts with low MAF (median 11.1 vs 6.6 months, HR 0.31 (0.12-0.83 p=0.019). This prognostic effect was maintained for low MAF pts in multivariable analysis (HR: 0.18 (0.06-0.56; p=0.03)). Pts treated with TAS had a worse prognosis in the multivariable analysis (HR 3.55 (1.05-12.02) p=0.042). Low MAF pts had longer PFS in multivariable analysis (HR 0.32 (0.12-0.88 p=0.027)). Table: 125P

Conclusions

In refractory mCRC pts, low plasma MAF levels correlate with better OS and PFS, indicating the potential of ctDNA as a prognostic biomarker. Despite pts treated with TASBev displaying poorer prognostic factors (as higher prevalence of liver disease) MAF remained as an independent prognostic indicator in our cohort. This plMAF cut-off needs to be validated in other cohorts of refractory mCRC pts.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

N. Saoudi Gonzalez: Financial Interests, Personal, Invited Speaker: Amgen; Other, Travel: Amgen, Merck. F. Salvà Ballabrera: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Invited Speaker: Sanofi, Merck, Servier, Roche, Terumo Company. F.J. Ros Montana: Financial Interests, Institutional, Invited Speaker: Sanofi; Other, Travel and accommodation expenses and Speaker: Amgen, Merck; Other, Travel and accommodation expenses: Pierre Fabre, Sanofi. I. Baraibar Argota: Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Other, Accommodation and travel expenses: Amgen, Merck, Sanofi, Servier. M. Rodriguez Castells: Financial Interests, Personal, Invited Speaker: Rovi; Other, Travel and accommodation: BMS, Merck; Other, Travel and accommodation: Amgen. R. Dienstmann: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Boehringer Ingelheim, Ipsen, Libbs, Lilly, Merck Sharp & Dohme, Roche, Sanofi, Servier, GSK, Takeda, Janssen, Gilead, Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Roche, Foundation Medicine; Financial Interests, Personal, Full or part-time Employment, Oncoclínicas is a private healthcare provider in Brazil. I work part time as Medical Director of the Precision Medicine and Big Data Initiative. We develop molecular tests (pathology and genomics) that are offered to patients treated in the organisation as part of support programs sponsored by pharmaceutical companies and I coordinate research activities with real-world clinico-genomics cohorts: Oncoclínicas; Financial Interests, Personal, Stocks/Shares: Trialing; Financial Interests, Personal, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Novartis, AstraZeneca, Daiichi Sankyo, GSK. J. Tabernero: Financial Interests, Personal, Advisory Board, scientific consultancy role: Orion Biotechnology, AstraZeneca, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd., Genentech Inc., Ikena Oncology, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Scandion Oncology, Ona Therapeutics, Sotio Biotech, Inspirna Inc, Scorpion Therapeutics, Tolremo Therapeutics, CARSgen Therapeutics, hC Bioscience Inc, Takeda Pharmaceuticals International AG, Alentis Therapeutics, Immodulon Therapeutics; Financial Interests, Personal, Invited Speaker, educational collaboration: Medscape Education, Physicians Education Resource (PER), PeerView Institute for Medical Education, Imedex/HMP; Financial Interests, Personal, Advisory Board: Cardiff Oncology, Aveo Oncology; Financial Interests, Personal, Stocks/Shares: Oniria Therapeutics, 1TRIALSP, Alentis Therapeutics, Pangaea Oncology; Financial Interests, Institutional, Research Grant, ACRCelerate: Colorectal Cancer Stratified: Fundación Científica de la Asociación Española Contra el Cáncer; Financial Interests, Institutional, Research Grant, OPTIMISTICC: Opportunity to Investigate the Microbiome’s Impact on Science and Treatment In Colorectal Cancer: Cancer Research UK; Financial Interests, Institutional, Funding, Clinical Trials & Research: Amgen Inc, AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb International Corporation, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd., Genentech Inc, Janssen-Cilag International NV, Merck Health KGaA, Merck, Sharp & Dohme de España, SA, Novartis Farmacéutica SA, PharmaMar SA, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA, Inc, BeiGene, Boehringer Ingelheim, Menarini, Merus N V, Pfizer, Mirati; Non-Financial Interests, Member of Board of Directors, Board of Directors: Cancer Core Europe, Spanish Association Against Cancer -AECC; Non-Financial Interests, Member of Board of Directors, General Assembly: Horizon Europe Cancer Mission; Non-Financial Interests, Leadership Role, External Scientific Committee: Institute for Health Research INCLIVA – Clinical Hospital of Valencia, IdiSNA –Universidad de Navarra; Non-Financial Interests, Leadership Role, Scientific Advisory Board: Spanish National Cancer Research Centre (CNIO); Non-Financial Interests, Advisory Role, International Scientific Evaluation Committee: Bosch Health Campus (BHC); Non-Financial Interests, Advisory Role, Review Board: National Decade Against Cancer (NCT) - German Consortium for Translational Cancer Research (DKTK); Non-Financial Interests, Advisory Role, Scientific Advisory Board: Karolinska Comprehensive Cancer Centre; Non-Financial Interests, Advisory Role, International Review Committee (IRC): Oncode Institute; Non-Financial Interests, Advisory Role, Scientific Advisory Board (SAB): Oslo University Hospital Comprehensive Cancer Centre (OUH CCC); Non-Financial Interests, Leadership Role, Governance Advisory Committee: European Organization for Research and Treatment of Cancer -EORTC; Non-Financial Interests, Leadership Role, Vice Chairman: World Innovative Networking (WIN) Consortium in Personalized Cancer Medicine; Non-Financial Interests, Other, Coordinating PI & Steering Committee Member. Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutical LP, Boehringer Ingelheim, MedImmune, Menarini, Merck Healthcare KGaA, Merck, Sharp & Dohme de España SA, Pfizer, Servier; Non-Financial Interests, Principal Investigator, Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutics LP, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb International Corporation, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd., Genentech Inc., HalioDX SAS, Hutchinson Medipharma, Janssen-Cilag International NV, MedImmune, Menarini, Merck Healthcare KGaA, Merck, Sharp & Dohme de España SA, Merus NV, Mirati, Novartis Farmacéutica SA, Pfizer, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA Inc; Non-Financial Interests, Other, Steering Committee Member. Clinical Trials & Research: Debiopharm International SA, F. Hoffmann-La Roche Ltd., Genentech Inc., HalioDX SAS, Hutchinson Medipharma, Janssen-Cilag International NV, Merus NV, Taiho Pharma USA Inc; Non-Financial Interests, Other, Coordinating PI. Clinical Trials & Research: Mirati; Non-Financial Interests, Member: AACR, ASCO, EACR, EORTC, SEOM; Other, President: Oncology Master Plan – Catalonia Department of Health; Other, Advisory Committee: Advisory Committee on Pharmaceutical Provision Financing under the Spanish National Health System. A. Vivancos: Financial Interests, Personal, Advisory Board: Roche, Bristol Meyers Squibb, Guardant Health, Bayer, Incyte; Financial Interests, Personal, Stocks/Shares: Reveal Genomics; Financial Interests, Institutional, Research Grant, Preclinical Research Grant: Bristol Meyers Squibb, Roche, Incyte. M.E. Elez Fernandez: Financial Interests, Personal, Advisory Board: Hoffmann-La Roche, Servier, Amgen, Merck Serono, Sanofi, Bayer, Pierre Fabre, MSD, Takeda, Boehringer Ingelheim, Cure Teq AG, Repare Therapeutics Inc., RIN Institute Inc., Janssen; Financial Interests, Personal, Invited Speaker: Organon, Novartis, Pfizer, BMS, Lilly, Medscape; Financial Interests, Personal, Other, Educational training: Seagen International GmbH; Financial Interests, Institutional, Funding: Hoffmann-La Roche Ltd., Sanofi Aventis Recherche & Développement, Amgen Inc., Boehringer Ingelheim, Novartis Farmacéutica SA, Bristol Myers Squibb International Corporation, BeiGene, HalioDX SAS, Janssen-Cilag SA, Merck Health KGaA, Merck Sharp & Dohme de España SA, PharmaMar SA, Servier, Taiho Pharma USA Inc., Hutchison MediPharma International, Menarini, Merus NV, Pfizer, Mirati, Array Biopharma Inc., AstraZeneca Pharmaceuticals LP, Celgene International SARL, Debiopharm International SA, Genentech Inc, MedImmune, AbbVie Deutschland GmbH & Co KG, Bayer Pharma AG, Bioncotech Therapeutics, S.L., BioNTech Rna Pharmaceuticals GmbH, BioNTech Small Molecules GmbH, Boehringer Ingelheim de España S.A., Daiichi Sankyo, Inc, Gercor, Hutchinson Medipharma Limited, Iovance Biotherapeutics, Inc., Janssen Research & Development, Menarini Ricerche SPA, Merck, Sharp & Dohme De España S.A., Nouscom SRL., Pledpharma AB, Redx Pharma PLC, Scandion Oncology, Seattle Genetics Inc., Sotio A.S., Wntresearch AB; Non-Financial Interests, Other, Coordinator of the SEOM + MIR Section of Residents and Young Assistants: Sociedad Española de Oncología Médica (SEOM); Non-Financial Interests, Other, Speaker of the ESMO Academy: European Society for Medical Oncology (ESMO); Non-Financial Interests, Other, Volunteer member of the ASCO Annual Meeting Scientific Program Committee: Developmental Therapeutics – Immunotherapy: American Society of Clinical Oncology (ASCO); Non-Financial Interests, Leadership Role, Member of the Scientific Program Committee and Developmental Therapeutics-Immunotherapy Track Leader, 2023-2024 term: American Society for Clinical Oncology (ASCO); Non-Financial Interests, Other, Member of the Scientific Committee 2024: European Society for Medical Oncology (ESMO); Other, Travel, accommodation, expenses: Roche, Merck Serono, Sanofi, Amgen, Array BioPharma, Servier, Bristol Myers Squibb. All other authors have declared no conflicts of interest.