Genotype-based selection of treatment of patients with advanced colorectal cancer (SETICC): a pharmacogenetic-based randomized phase II trial
Por:
Abad, A, Martinez-Balibrea, E, Vieitez, JM, Alonso-Orduna, V, Alfonso, PG, Manzano, JL, Massuti, B, Benavides, M, Carrato, A, Zanui, M, Gallego, J, Gravalos, C, Conde, V, Provencio, M, Valladares-Ayerbes, M, Salazar, R, Sastre, J, Montagut, C, Rivera, F and Aranda, E
Publicada:
1 feb 2018
Resumen:
Background: There has been little progress toward personalized therapy for patients with metastatic colorectal cancer (mCRC). TYMS-30 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-30UTR 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 9.4months 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 19.1months, 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-30UTR and ERCC1-118 polymorphisms warrants further investigation in patients with mCRC.
Filiaciones:
Abad, A:
Catalan Inst Oncol, Med Oncol Serv, Badalona, Spain
:
Catalan Inst Oncol, Med Oncol Serv, Badalona, Spain
Germans Trias & Pujol Res Inst, PMPPC, Badalona, Spain
Catalan Inst Oncol, ProCURE Program Canc Therapeut Resistance, Badalona, Spain
Vieitez, JM:
Hosp Univ Cent Asturias, Med Oncol Serv, Oviedo, Spain
Alonso-Orduna, V:
Hosp Univ Miguel Servet, Med Oncol, Zaragoza, Spain
Alfonso, PG:
Hosp Gen Univ Gregorio Maranon, Med Oncol Serv, Madrid, Spain
:
Catalan Inst Oncol, Med Oncol Serv, Badalona, Spain
Massuti, B:
Hosp Gen Univ Alicante, Med Oncol Serv, Alicante, Spain
Benavides, M:
Hosp Univ Reg & Virgen Victoria, Med Oncol Serv, Malaga, Spain
Carrato, A:
Alcala Univ, CIBERONC, Ramon y Cajal Univ Hosp, Ramon y Cajal Inst Hlth Res IRYCIS, Madrid, Spain
Zanui, M:
Hosp Mataro, Med Oncol Serv, Barcelona, Spain
Gallego, J:
Hosp Gen Univ Elche, Med Oncol Serv, Alicante, Spain
Gravalos, C:
Hosp Univ 12 Octubre, Med Oncol Serv, Madrid, Spain
Conde, V:
Hosp Virgen de las Nieves, Med Oncol Serv, Granada, Spain
Provencio, M:
Hosp Puerta Hierro, Med Oncol Serv, Madrid, Spain
Valladares-Ayerbes, M:
Complexo Hosp Univ A Coruna, Med Oncol Serv, La Coruna, Spain
Salazar, R:
Inst Invest Biomed Bellvitge, ONCOBELL Program, Barcelona, Spain
CIBERONC, ICO, Dept Med Oncol, Barcelona, Spain
Sastre, J:
Hosp Clin San Carlos, Med Oncol Serv, Inst Invest Hosp Clin San Carlos IdISSC, CIBERONC, Madrid, Spain
Montagut, C:
Hosp del Mar, Med Res Inst, CIBERONC, Med Oncol Serv, Barcelona, Spain
Rivera, F:
Hosp Marques Valdecilla, Med Oncol Serv, Santander, Spain
Aranda, E:
Univ Cordoba, Med Oncol Serv, Inst Maimonides Invest Biomed Cordoba IMIBIC, Reina Sofia Hosp, Cordoba, Spain
Inst Salud Carlos III, CIBERONC, Madrid, Spain
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