Abstract 384P
Background
Plasma-based circulating tumour DNA (ctDNA) provides a minimally invasive, contemporaneous assessment of genomic alterations (GAs) and captures tumour heterogeneity. We compare GAs identified in ctDNA and archival tissue in patients (pts) with metastatic colorectal cancer (CRC) recruited to the Tumour Characterisation to Guide Experimental Targeted Therapy (TARGET) trial, aiming to match pts to early-phase cancer clinical trials (EPCCT).
Methods
Archival tumour tissue was analysed using next generation sequencing (NGS) panels (24 genes), and plasma-based ctDNA was analysed using a local research NGS panel (641 genes). Results were discussed in a molecular tumour board (MTB) to define actionability. Factors associated with the likelihood of having additional GAs in ctDNA were explored using logistic regression analysis and odds ratio (OR).
Results
101 pts with CRC were recruited to TARGET. The median age was 56 years and 61% were male. Pts had NGS testing panels from primary (70%) or metastatic (30%) archival tumour tissue. The median age of archival tissue tested was 25 months (range 0-117 months) and 98% of pts received active treatment in the intervening time. Tissue and ctDNA NGS identified clinically relevant GAs in 90% and 79% of pts respectively, with a median of 2 GAs per pt. The most common GAs in ctDNA were TP53 (53%), KRAS (47%), APC (44%), and PIK3CA (12%). There was poor concordance of identified GAs between tissue and ctDNA (agreement=66.3%, Cohen's k<0, p=0.91). 23% of pts had clinically relevant GAs in ctDNA that were not identified in tissue, the commonest being KRAS (29%). There was no association between the presence of additional GAs in ctDNA with number of treatment lines (OR:1.23, p= 0.32), age of archival tissue (OR: 1.01, p= 0.91) or primary vs. metastatic archival tissue site (OR: 0.34, p= 0.11). The presence of liver metastases was associated with a higher likelihood of concordance between tissue and ctDNA NGS (OR: 3.5, p= 0.03). Overall, ctDNA-derived GAs were considered actionable in 51% of pts. Of those, 28% were a potential match for an EPCCT.
Conclusions
Plasma-based ctDNA can be used as a contemporaneous tool to identify actionable GAs and guide treatment options for pts with metastatic CRC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Research and Innovation Department, Christie NHS Foundation Trust.
Funding
The Christie Charity.
Disclosure
A. Ortega Franco: Financial Interests, Personal, Invited Speaker, clinical case presentation: MSD. F. Thistlethwaite: Financial Interests, Personal, Advisory Board, honoraria: Bayer; Financial Interests, Personal, Advisory Board, Ad board: BMS, Zelluna; Financial Interests, Personal, Advisory Board, Ad boards: GSK; Financial Interests, Personal, Advisory Board, Adboard/consultancy: Tknife; Financial Interests, Personal, Advisory Board: Adicet, Janssen, EnaraBio, Immatics, Ixaka; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Other, iMATCH is a 12 partner consortium funded by not for profit Innovate UK (UK government body) partners include commercial, clinical and academic institutes. I am director and my salary (0.2WTE) is supported through this work as a grant to my institution (The Christie NHS foundation trust - not for profit NHS hospital) from IUK: iMATCH director; Financial Interests, Institutional, Officer, Clinical lead for this 10 partner consortium of clinical academic and commercial partners. My salary is partly supported (approx. 0.05WTE) through this by a grant paid by Innovate UK (a NFP government body) to my institution (The Christie NHS foundation trust a NFP UK hospital): SAMPLE; Financial Interests, Institutional, Invited Speaker: Pfizer, GenMab, synthon, CytomX, Incyte, Janssen, Adaptimmune, Aveo, BMS, GSK, Roche, Abbvie, Immunocore, Achilles ltd, Agalimmune Ltd, Kymab Ltd, Chugai, Millenium Pharmaceuticals/Takeda, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca; Non-Financial Interests, Other, Panel member for a funding committee (MRC is a UK government NFP organisation): MRC DPFS panel member. D.M. Graham: Financial Interests, Personal, Advisory Board, Consulting role on advisory board: clinigen; Financial Interests, Personal, Invited Speaker: Cancer Drug Development Fund; Financial Interests, Personal, Advisory Board: McCann Health; Financial Interests, Institutional, Invited Speaker, Institutional funding from study: MSD, Codiak Biosciences, Starpharma, Faron Pharmaceuticals, Synthon, Janssen; Financial Interests, Institutional, Other, Sub-I: Institutional funding from study: AstraZeneca, Roche, BerGenBio, GlaxoSmithKline, Bayer, Bicycle pharmaceuticals, Carrick, Taiho pharmaceuticals, CytomX Therapeutics, RedX Pharma PLC, Eisai Inc, Octimet, Orion Pharma, Kinex pharmaceuticals, Boehringer Ingelheim, BMS, Turning Point Therapeutics, Immutep, Agalimmune, Kymab, Blueprint, Astellas, Cellcentric, UCB Biopharma USL, Eli Lily, Seagen, Repare therapeutics, Timepoint Therapeutics, Astex, Stemline, Crescendo Biologics Ltd, ADC Therapeutics, Genentech, Avacta Life Sciences Ltd, Nurix Therapeutics Inc; Financial Interests, Institutional, Other, Sub-I: Institutional finding from study: Chugai Pharmaceuticals; Financial Interests, Institutional, Invited Speaker: Incyte. L. Carter: Financial Interests, Personal, Other, Consultancy: Bicycle Therapeutics, Boehringer Ingelheim, Athenex; Financial Interests, Institutional, Invited Speaker: Boehringer Ingelheim, Bicycle Therapeutics, Cellcentric, Eli Lily, Athenex, Lupin Limited, Repare Therapeutics, Cytomx therapeutics, EMD Serono/Merck KGaA, Sierra Oncology. G.J. Burghel: Financial Interests, Personal, Invited Speaker, I was compensated for educational presentations: AstraZeneca. M.G. Krebs: Financial Interests, Personal, Other, Research Support/PI: Astex, AstraZeneca, Bayer, BerGenBio, Blueprint, Carrick, Immutep, Incyte, Jannsen, Lilly, Merck, MSD, Nurix, Octimet, Roche, Seattle Genetics, Turning Point Therapeutics; Financial Interests, Personal, Other, Consultant: Janssen, OM Pharma, Roche; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Janssen, Roche; Financial Interests, Personal, Other, Honoraria: BerGenBio, Immutep, Janssen, Roche; Financial Interests, Personal, Advisory Board: Bayer, Guardant Health, Janssen, Roche, Seattle Genetics. N. Cook: Financial Interests, Institutional, Invited Speaker: Roche, Taiho, Roche, Astra Zeneca, RedX, Orion, Avacta, Bayer, Eisai, UCB, Starpharma, Boeringher, Stemline, Ergomed; Non-Financial Interests, Advisory Role: Roche. All other authors have declared no conflicts of interest.