1. Comprehensive genomic profiling by liquid biopsy captures tumor heterogeneity and identifies cancer vulnerabilities in patients with RAS/BRAF V600E wild-type metastatic colorectal cancer in the CAPRI 2-GOIM trial.
- Author
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Ciardiello D, Boscolo Bielo L, Napolitano S, Martinelli E, Troiani T, Nicastro A, Latiano TP, Parente P, Maiello E, Avallone A, Normanno N, Pisconti S, Nisi C, Bordonaro R, Russo AE, Tamburini E, Toma I, Lotesoriere C, Vallarelli S, Zampino MG, Fazio N, Curigliano G, De Vita F, Ciardiello F, and Martini G more...
- Subjects
- Humans, Liquid Biopsy methods, Female, Male, Mutation, Cetuximab administration & dosage, Cetuximab therapeutic use, Aged, Middle Aged, Biomarkers, Tumor genetics, Proto-Oncogene Proteins p21(ras) genetics, GTP Phosphohydrolases genetics, Genetic Heterogeneity, Prospective Studies, Genomics methods, Neoplasm Metastasis, Adult, Membrane Proteins genetics, Gene Expression Profiling, Colorectal Neoplasms genetics, Colorectal Neoplasms drug therapy, Colorectal Neoplasms pathology, Proto-Oncogene Proteins B-raf genetics, Circulating Tumor DNA genetics, Circulating Tumor DNA blood
- Abstract
Background: Emerging evidence supports tumor tissue-based comprehensive genomic profiling (CGP) in metastatic colorectal cancer (mCRC). Data on liquid biopsy-based circulating tumor DNA (ctDNA) CGP are scarce and mainly retrospective. Prospective comparison between the two tests is not currently available., Materials and Methods: The CAPRI 2-GOIM trial investigates efficacy and safety of ctDNA-driven, cetuximab-based sequence of three treatment lines in patients with RAS/BRAF
V600E wild-type (WT) mCRC, as determined by the local laboratory. Before first-line therapy, CGP is carried out with FoundationOne (F1) CDx and F1 Liquid (F1L) CDx (324 genes) on tumor tissue DNA and plasma ctDNA, respectively., Results: For 2/207 (0.96%) patients, no ctDNA was detected by F1L CDx. No patient displayed tumor fraction (TF) below 1%, whereas elevated ctDNA (TF ≥ 10%) was detected among 140/205 (68.3%) patients. One thousand and thirteen genomic variants were identified. F1L CDx found KRAS, NRAS, or BRAFV600E alterations in 19 patients, whose tumors were classified as RAS/BRAFV600E WT by the local laboratory. Both F1 CDx and F1L CDx were available for 164/205 (80%) patients. A concordance of 61.4% between the two tests was observed. The concordance increased to 72.7% for F1L CDx with TF ≥ 10%. Concordance for genes potentially involved in anti-epidermal growth factor receptor resistance was found in 137/164 (83%) patients, increasing to 91.5% for F1L CDx with TF ≥ 10%. A higher number of genomic alterations was detected by F1L CDx compared with F1 CDx, including six cases with KRAS and NRAS alterations. Overall, 109/205 (53.2%) patients displayed at least one actionable genomic alteration (I to IIIB), according to the European Society for Medical Oncology Scale for Clinical Actionability of Molecular Targets (ESCAT)., Conclusion: Baseline liquid biopsy-based CGP is feasible, has high concordance with tumor tissue-based CGP, could better recapitulate tumor heterogeneity, and is clinically informative by identifying additional actionable genomic alterations in approximately half of RAS/BRAFV600E WT mCRC patients., (Copyright © 2024 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.) more...- Published
- 2024
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