A Abad1, E Martínez-Balibrea2, J M Viéitez3, V Alonso-Orduña4, P García Alfonso5, J L Manzano1, B Massutí6, M Benavides7, A Carrato8, M Zanui9, J Gallego10, C Grávalos11, V Conde12, M Provencio13, M Valladares-Ayerbes14, R Salazar15, J Sastre16, C Montagut17, F Rivera18, E Aranda19. 1. Medical Oncology Service, Catalan Institute of Oncology, Badalona, Spain. 2. Medical Oncology Service, Catalan Institute of Oncology, Badalona, Spain; Program of Predictive and Personalized Medicine of Cancer (PMPPC), Germans Trias i Pujol Research Institute, Badalona, Spain; ProCURE (Program Against Cancer Therapeutic Resistance), Catalan Institute of Oncology, Badalona, Spain. Electronic address: embalibrea@iconcologia.net. 3. Medical Oncology Service, Hospital Universitario Central de Asturias, Oviedo, Spain. 4. Medical Oncology Service, Hospital Universitario Miguel Servet, Zaragoza, Spain. 5. Medical Oncology Service, Hospital General Universitario Gregorio Marañón, Madrid, Spain. 6. Medical Oncology Service, Hospital General Universitario de Alicante, Alicante, Spain. 7. Medical Oncology Service, Hospital Universitario Regional y Virgen de la Victoria, Málaga, Spain. 8. Ramon y Cajal University Hospital, Ramon y Cajal Institute for Health Research - IRYCIS, Alcala University, CIBERONC, Madrid, Spain. 9. Medical Oncology Service, Hospital de Mataró, Barcelona, Spain. 10. Medical Oncology Service, Hospital General Universitario de Elche, Alicante, Spain. 11. Medical Oncology Service, Hospital Universitario 12 de Octubre, Madrid, Spain. 12. Medical Oncology Service, Hospital Virgen de las Nieves, Granada, Spain. 13. Medical Oncology Service, Hospital Puerta de Hierro, Madrid, Spain. 14. Medical Oncology Service, Complexo Hospitalario Universitario A Coruña, La Coruña, Spain. 15. ONCOBELL program, Institut d'Investigació Biomédica de Bellvitge, Barcelona, Spain; Medical Oncology Department, Catalan Institute of Oncology (ICO), CIBERONC, L'Hospitalet de Llobregat, Barcelona, Spain. 16. Medical Oncology Service, Hospital Clínico San Carlos, Instituto de investigación Hospital Clínico San Carlos (IdISSC), CIBERONC, Madrid, Spain. 17. Medical Oncology Service, Hospital del Mar Medical Research Institute, CIBERONC, Barcelona, Spain. 18. Medical Oncology Service, Hospital Marqués de Valdecilla, Santander, Spain. 19. Medical Oncology Service, Instituto Maimónides del Investigación Biomédica de Córdoba (IMIBIC), Reina Sofía Hospital, University of Córdoba, Córdoba, Spain; CIBERONC, Instituto de Salud Carlos III, Madrid, Spain.
Abstract
Background: There has been little progress toward personalized therapy for patients with metastatic colorectal cancer (mCRC). TYMS-3' untranslated region (UTR) 6 bp ins/del and ERCC1-118C/T polymorphisms were previously reported to facilitate selecting patients for fluoropyrimidine-based treatment in combination with oxaliplatin as first-line therapy. We assessed the utility of these markers in selecting therapy for patients with mCRC. Patients and methods: This randomized, open-label phase II trial compared bevacizumab plus XELOX (control) versus treatment tailored according to TYMS-3'UTR 6 bp ins/del and ERCC1-118C/T polymorphisms. Patients randomized to the experimental treatment received bevacizumab plus FUOX, FUIRI, XELIRI, or XELOX depending on their combination of favorable polymorphisms for FUOX treatment (TYMS-3'UTR ins/del or del/del; ERCC1-118T/T). Progression-free survival (PFS) was the primary end point. Results: Overall, 195 patients were randomized (control n = 65; experimental n = 130). The primary objective was not met: median PFS was 9.4 months in the control group and 10.1 months in the experimental group (P = 0.745). Median overall survival was similar in both groups (16.5 versus 19.1 months, respectively; P = 0.797). Patients in the experimental group had a significantly higher overall response rate (ORR; 65% versus 47% in the control group; P = 0.042) and R0 resection rate (86% versus 44%, respectively; P = 0.018). Neuropathy, hand-foot syndrome, thrombocytopenia, and dysesthesia were significantly less common in the experimental group. Conclusions: This study did not show survival benefits after treatment personalization based on polymorphisms in mCRC. However, the improved ORR and R0 resection rate and fewer disabling toxicities suggest that tailoring therapy by TYMS-3'UTR and ERCC1-118 polymorphisms warrants further investigation in patients with mCRC. ClinicalTrials.gov: NCT01071655.
RCT Entities:
Background: There has been little progress toward personalized therapy for patients with metastatic colorectal cancer (mCRC). TYMS-3' untranslated region (UTR) 6 bp ins/del and ERCC1-118C/T polymorphisms were previously reported to facilitate selecting patients for fluoropyrimidine-based treatment in combination with oxaliplatin as first-line therapy. We assessed the utility of these markers in selecting therapy for patients with mCRC. Patients and methods: This randomized, open-label phase II trial compared bevacizumab plus XELOX (control) versus treatment tailored according to TYMS-3'UTR 6 bp ins/del and ERCC1-118C/T polymorphisms. Patients randomized to the experimental treatment received bevacizumab plus FUOX, FUIRI, XELIRI, or XELOX depending on their combination of favorable polymorphisms for FUOX treatment (TYMS-3'UTR ins/del or del/del; ERCC1-118T/T). Progression-free survival (PFS) was the primary end point. Results: Overall, 195 patients were randomized (control n = 65; experimental n = 130). The primary objective was not met: median PFS was 9.4 months in the control group and 10.1 months in the experimental group (P = 0.745). Median overall survival was similar in both groups (16.5 versus 19.1 months, respectively; P = 0.797). Patients in the experimental group had a significantly higher overall response rate (ORR; 65% versus 47% in the control group; P = 0.042) and R0 resection rate (86% versus 44%, respectively; P = 0.018). Neuropathy, hand-foot syndrome, thrombocytopenia, and dysesthesia were significantly less common in the experimental group. Conclusions: This study did not show survival benefits after treatment personalization based on polymorphisms in mCRC. However, the improved ORR and R0 resection rate and fewer disabling toxicities suggest that tailoring therapy by TYMS-3'UTR and ERCC1-118 polymorphisms warrants further investigation in patients with mCRC. ClinicalTrials.gov: NCT01071655.
Authors: Elena De Mattia; Rossana Roncato; Chiara Dalle Fratte; Fabrizio Ecca; Giuseppe Toffoli; Erika Cecchin Journal: Cancer Drug Resist Date: 2019-03-19
Authors: Jennifer G Le-Rademacher; Camden L Lopez; Rahul Kanwar; Brittny Major-Elechi; Alexej Abyzov; Michaela S Banck; Terry M Therneau; Jeff A Sloan; Charles L Loprinzi; Andreas S Beutler Journal: J Neurol Sci Date: 2020-01-14 Impact factor: 3.181