| Autor: |
Gambaro K; Canadian National Centres of Excellence-Exactis Innovations, Montreal, QC H3T 1Y6, Canada.; Consortium de Recherche en Oncologie Clinique du Québec (Q-CROC), Quebec, QC G1V 3X8, Canada.; Segal Cancer Centre-Jewish General Hospital, Montreal, QC H3T 1E2, Canada., Marques M; Canadian National Centres of Excellence-Exactis Innovations, Montreal, QC H3T 1Y6, Canada.; Segal Cancer Centre-Jewish General Hospital, Montreal, QC H3T 1E2, Canada., McNamara S; Canadian National Centres of Excellence-Exactis Innovations, Montreal, QC H3T 1Y6, Canada.; Consortium de Recherche en Oncologie Clinique du Québec (Q-CROC), Quebec, QC G1V 3X8, Canada., Couetoux du Tertre M; Canadian National Centres of Excellence-Exactis Innovations, Montreal, QC H3T 1Y6, Canada.; Consortium de Recherche en Oncologie Clinique du Québec (Q-CROC), Quebec, QC G1V 3X8, Canada., Hoffert C; Canadian National Centres of Excellence-Exactis Innovations, Montreal, QC H3T 1Y6, Canada.; Consortium de Recherche en Oncologie Clinique du Québec (Q-CROC), Quebec, QC G1V 3X8, Canada.; Segal Cancer Centre-Jewish General Hospital, Montreal, QC H3T 1E2, Canada., Srivastava A; Canadian National Centres of Excellence-Exactis Innovations, Montreal, QC H3T 1Y6, Canada.; Consortium de Recherche en Oncologie Clinique du Québec (Q-CROC), Quebec, QC G1V 3X8, Canada.; Segal Cancer Centre-Jewish General Hospital, Montreal, QC H3T 1E2, Canada., Schab A; Canadian National Centres of Excellence-Exactis Innovations, Montreal, QC H3T 1Y6, Canada.; Consortium de Recherche en Oncologie Clinique du Québec (Q-CROC), Quebec, QC G1V 3X8, Canada., Alcindor T; McGill University Health Centre, Montreal, QC H4A 3J1, Canada., Langleben A; St. Mary's Hospital, Montreal, QC H3T 0A2, Canada., Sideris L; Hôpital Maisonneuve Rosemont, Montreal, QC H1T 2M4, Canada., Abdelsalam M; The Moncton Hospital, Moncton, NB E1C 6Z8, Canada., Tehfe M; Hematology-Oncology, Oncology Center-Centre Hospitalier de l'Université de Montreal, Montreal, QC H2X 0C1, Canada., Couture F; Hôtel-Dieu de Québec, Quebec, QC G1R 2J6, Canada., Batist G; Segal Cancer Centre-Jewish General Hospital, Montreal, QC H3T 1E2, Canada., Kavan P; Segal Cancer Centre-Jewish General Hospital, Montreal, QC H3T 1E2, Canada. |
| Abstrakt: |
Single-agent regorafenib is approved in Canada for metastatic colorectal cancer (mCRC) patients who have failed previous lines of therapy. Identifying prognostic biomarkers is key to optimizing therapeutic strategies for these patients. In this clinical study (NCT01949194), we evaluated the safety and efficacy of single-agent regorafenib as a second-line therapy for mCRC patients who received it after failing first-line therapy with an oxaliplatin or irinotecan regimen with or without bevacizumab. Using various omics approaches, we also investigated putative biomarkers of response and resistance to regorafenib in metastatic lesions and blood samples in the same cohort. Overall, the safety profile of regorafenib seemed similar to the CORRECT trial, where regorafenib was administered as ≥ 2 lines of therapy. While the mutational landscape showed typical mutation rates for the top five driver genes (APC, KRAS, BRAF, PIK3CA, and TP53), KRAS mutations were enriched in intrinsically resistant lesions. Additional exploration of genomic-phenotype associations revealed several biomarker candidates linked to unfavorable prognoses in patients with mCRC using various approaches, including pathway analysis, cfDNA profiling, and copy number analysis. However, further research endeavors are necessary to validate the potential utility of these promising genes in understanding patients' responses to regorafenib treatment. |
