Comprehensive genomic profiling by liquid biopsy portrays metastatic colorectal cancer mutational landscape to predict antitumor efficacy of FOLFIRI plus cetuximab in the CAPRI-2 GOIM trial
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Le résumé fourni par la source
BACKGROUND: Limited evidence is currently available on the role of liquid biopsy (LBx) in predicting the efficacy of anti-epidermal growth factor receptor (EGFR) therapies in metastatic colorectal cancer (mCRC). METHODS: The CAPRI-2 GOIM is a phase II trial investigating the use of LBx-comprehensive genomic profiling (CGP)-guided, cetuximab-based treatment through three subsequent lines of therapy in patients with RAS/BRAF wild-type (WT) mCRC. LBx-CGP is carried out at baseline and at progressive disease to first- and second-line therapies. In case of RAS/BRAF WT circulating tumor DNA at progressive disease, EGFR therapeutic blockade is continued by combining cetuximab with a different chemotherapy backbone. The primary endpoint is overall response rate (ORR) by RECIST 1.1 criteria. Tumor molecular characteristics by LBx-CGP are correlated with treatment efficacy. RESULTS: One hundred and ninety-two RAS/BRAF WT microsatellite stable mCRC patients treated with FOLFIRI plus cetuximab with baseline LBx-CGP and assessable for response were included in the analysis. One hundred and thirty-seven patients with WT tumors for potential anti-EGFR drug resistance genes (RAS/BRAF/EGFR/PIK3CA/MAP2K1/MET/RET/ALK/ROS1/NTRK/NF1/FGFR, and HER2 amplification; 'negatively hyper-selected' cases) had 78.1% ORR compared with 54.5% ORR for patients with mutations [odds ratio 2.95, 95% confidence interval (CI) 1.44-6.10, P = 0.001]. 'Negatively hyper-selected' patients had median progression-free survival of 12.35 months (95% CI 10.58-15.4 months) compared with 8.68 months (95% CI 4.87-12.1 months) for patients with mutations (hazard ratio 0.64, 95% CI 0.44-0.92, P = 0.017). High cancer cell clonality of pathogenic variants (PVs) correlated with worse median progression-free survival (3.55 months, 95% CI 2.57 months to NE) compared with low cancer cell clonality of PV (9.63 months, 95% CI 7.16 months to NE, P = 0.21). After first-line therapy failure, approximately one out of five patients had acquired PVs of potential anti-EGFR drug resistance genes, whereas RAS/BRAF WT circulating tumor DNA was maintained in most patients (78.5%). CONCLUSIONS: These results support the integration of LBx-CGP for implementing the efficacy and for optimizing the use of anti-EGFR therapies in RAS/BRAF WT mCRC.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Comprehensive genomic profiling by liquid biopsy portrays metastatic colorectal cancer mutational landscape to predict antitumor efficacy of FOLFIRI plus cetuximab in the CAPRI-2 GOIM trial
- Date Crossref
- 01/04/2025
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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European Institute of Oncology Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors pays non établi dans la noticeÉtablissement de santé
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University of Milan European Institute of Oncology pays non établi dans la noticeUniversité ou école supérieure
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University of Campania "Luigi Vanvitelli" pays non établi dans la noticeUniversité ou école supérieure
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Casa Sollievo della Sofferenza pays non établi dans la noticeÉtablissement de santé
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Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" pays non établi dans la noticeÉtablissement de santé
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Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors — European Institute of Oncology, European Institute of Oncology — University of Milan et University of Campania "Luigi Vanvitelli", avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.