Comprehensive genomic profiling of circulating tumor DNA for treatment recommendation: A sub-project of the IMPRESS-Norway trial

BackgroundAs precision oncology is rapidly evolving, comprehensive tools for the identification of genomic alterations indicating response and resistance to therapy are increasingly important for treatment selection. We investigated the clinical utility of comprehensive genomic profiling (CGP) of circulating tumor DNA (ctDNA) as a minimally invasive approach for actionable biomarker identification.MethodsIn the IMPRESS-Norway trial (NCT04817956), patients with treatment-refractory advanced cancer are screened for actionable biomarkers by the tissue CGP assay TruSight Oncology 500, performed as part of the public healthcare service. In this sub-project, a subset of patients was screened in parallel with the FoundationOne Liquid CDx assay using ctDNA from plasma. Findings from both assays were discussed at the National Molecular Tumor Board for actionable biomarker identification and matched targeted therapy recommendation.ResultsFrom April 2021 to June 2023, a total of 529 patients referred for tissue CGP were enrolled in IMPRESS-Norway and included for ctDNA analysis. Of these, 508 (96.0 %) ctDNA reports were received, and 490 (92.6 %) tissue analyses were performed. Turnaround time was significantly shorter for ctDNA (median = 16 days, IQR: 14-20) than for tissue analysis (median = 39 days, IQR: 33-48) with a median difference of 21 days (p<0.001). Of patients with a ctDNA report, a total of 141 patients (27.8 %) were identified harboring ≥1 actionable biomarkers matching a drug in the trial. In 59/141 patients (41.8 %), these biomarkers were revealed in both ctDNA and tissue, and in 63/141 patients (44.7 %), they were found in tissue only. Of interest, in 19/141 patients (13.5 %) the biomarkers were detected in ctDNA only, including 4 cases without tissue CGP. The utility of ctDNA was promising in patients with breast, colorectal and urinary tract cancer, but expectedly limited in patients with CNS cancer.ConclusionsCGP of ctDNA as a diagnostic tool for treatment recommendation improves the access to targeted therapy for advanced cancer patients, when added to tissue CGP. For selected patient groups, ctDNA CGP alone could be sufficient as the primary diagnostic approach enabling a faster therapy initiation.Clinical trial identificationEudraCT 2020-004414-35; NCT04817956.Legal entity responsible for the studyOslo University Hospital.FundingIMPRESS-Norway is sponsored by Oslo University Hospital. The Regional Health Authorities of Norway through the KlinBeForsk National Clinical Trials Programme, the Norwegian Cancer Society, The Norwegian Radium Hospital Research Foundation and NordForsk have provided financial support. Roche, Novartis, Eli Lilly, AstraZeneca, Incyte, Merck and GSK provide the study drugs and financial support. Roche has sponsored and conducted the FoundationOne Liquid CDx analyses.DisclosureI. Dyvik: Financial Interests, Institutional, Other, Sponsored and conducted FoundationOne Liquid CDx tests for a subproject in my PhD studies.: Roche; Financial Interests, Institutional, Other, Sponsored TSO500 ctDNA assays for a subproject in my PhD studies.: Illumina. T.K.K. Guren: Financial Interests, Institutional, Other, Honoraria: Pierre Fabre, Daiichi Sankyo; Financial Interests, Institutional, Local PI: Genentech/Roche, MSD, Merus, Pfizer, Ultimovacs, Eli Lilly/Loxo, Novartis, Boehringer Ingelheim. K. Puco: Financial Interests, Personal, Advisory Board, Both advisory board and invited speaker: Astellas Pharma, MSD, Bayer Norway, Pfizer AS; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb (BMS), Ipsen, Janssen-Cilaq; Financial Interests, Institutional, Funding: AstraZeneca, Roche, Novartis, Eli Lilly, Incyte, Merck, Illumina. S. Brabrand: Financial Interests, Personal, Invited Speaker: Astellas. E.S. Blix: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: Eli Lilly; Financial Interests, Personal, Invited Speaker: Novartis, Pfizer, Pierre Fabre, Roche. A. Flobak: Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Pfizer, Pierre Fabre, Amgen, Bayer. K. Tasken: Financial Interests, Personal, Advisory Board, Company established based on innovation in my lab. Holds stock and Scientific advisor: Serca Pharmaceuticals; Financial Interests, Personal, Stocks/Shares, Stock and Stock options, and royalty agreement through Oslo UniversityHospital/University of Oslo Tech Transfer Office Inven2 AS.: Serca Pharmaceuticals; Financial Interests, Personal, Stocks/Shares, Stock.: Ledidi; Financial Interests, Personal, Royalties, Stock and Stock options, and royalty agreement through Oslo UniversityHospital/University of Oslo Tech Transfer Office Inven2 AS.: Serca Pharmaceuticals; Financial Interests, Institutional, Steering Committee Member, IMPRESS-Norway trial Trial Management & Steering Committee: Roche; Financial Interests, Institutional, Steering Committee Member, IMPRESS Norway trial Trial Management & Steering Committee: Novartis, Lilly, Incyte, Merck KGaA, AstraZeneca, Illumina. A. Helland: Financial Interests, Institutional, Advisory Board, Advisory boards: Jansen, Takeda, AstraZeneca, AbbVie, Roche, BMS, Pfizer, MSD, Bayer, Lilly, Medicover; Financial Interests, Institutional, Invited Speaker, talks at meetings: AstraZeneca, Roche, AbbVie, Pfizer; Financial Interests, Institutional, Coordinating PI, BMS provides drug to patients in an investigator initiated clinical trial: BMS; Financial Interests, Institutional, Coordinating PI, Ultimovacs provides drug and funds for investigator initiated clinical trial: Ultimovacs; Financial Interests, Institutional, Coordinating PI, AstraZeneca provides drug and funds for investigator initiated clinical trial: AstraZeneca; Financial Interests, Institutional, Coordinating PI, Roche provides drug and funds for investigator initiated clinical trial: Roche; Financial Interests, Institutional, Coordinating PI, Novartis provides drug and funds for clinical trial: Novartis; Financial Interests, Institutional, Coordinating PI, Eli Lilly provides drug and funds for clinical study: Eli Lilly; Financial Interests, Institutional, Coordinating PI, Incyte provides drug and funds for clinical study: Incyte; Financial Interests, Institutional, Coordinating PI, Illumina provides assays for patients in a clinical trial: Illumina; Financial Interests, Institutional, Coordinating PI, GSK provides drug and funds for investigator initiated clinical trial: GSK; Non-Financial Interests, Other, Board member in the patient organisation until 2022. Provides advice and gives talks.: The lung cancer patients organisation. H.E..G. Russnes: Financial Interests, Institutional, Invited Speaker, Speaker on Illumina satellite meeting (ESMO 2022): Illumina; Financial Interests, Institutional, Advisory Board, Novartis satellite meeting, Nordic Lung Cancer meeting, 2022: Novartis; Financial Interests, Institutional, Other, Debate, precision medicine, Oslo 2022: Merck; Financial Interests, Institutional, Other, Participation, round table, Cholangiocarcinoma; Nordic meeting 2021: Incyte; Financial Interests, Institutional, Coordinating PI, Funding of 500 FMliquid test to patients in the IMPRESS-Norway trial: Roche Norway; Financial Interests, Institutional, Coordinating PI, Funding of TSO500 liquid tests for 500 patients in the IMPRESS-Norway trial: Illumina; Financial Interests, Institutional, Coordinating PI, Collaboration within the MATRIX constortium: Oxford Nanopore; Non-Financial Interests, Leadership Role, InPreD is an establishment in the public health care, securing disciplinary work when implementing precision diagnostics for cancer.: National Infrastructure for Precision Diagnostics (InPreD); Non-Financial Interests, Leadership Role, A network structure established as part of the public health care system, to share knowledge, build competence and work with harmonisation and standardisation to implement precision medicine.: National Competence Network for Precision Medicine; Non-Financial Interests, Leadership Role, Head of working group for molecular pathology and for the Norwegian association for molecular pathology: The Norwegian Association of Pathology. All other authors have declared no conflicts of interest.