Maintenance treatment with capecitabine and bevacizumab versus observation in metastatic colorectal cancer: updated results and molecular subgroup analyses of the phase 3 CAIRO3 study.

Autor:	Goey KKH; Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht., Elias SG; Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht., van Tinteren H; Department of Biometrics, Netherlands Cancer Institute Amsterdam - Antoni van Leeuwenhoek Hospital, Amsterdam., Laclé MM; Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht., Willems SM; Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht., Offerhaus GJA; Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht., de Leng WWJ; Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht., Strengman E; Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht., Ten Tije AJ; Department of Medical Oncology, Amphia Hospital, Breda., Creemers GM; Department of Medical Oncology, Catharina Hospital, Eindhoven., van der Velden A; Department of Medical Oncology, Tergooi Hospital, Hilversum., de Jongh FE; Department of Medical Oncology, Ikazia Hospital, Rotterdam., Erdkamp FLG; Department of Medical Oncology, Zuyderland MC, Heerlen-Sittard., Tanis BC; Department of Medical Oncology, Groene Hart Hospital, Gouda., Punt CJA; Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands., Koopman M; Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht.
Jazyk:	angličtina
Zdroj:	Annals of oncology : official journal of the European Society for Medical Oncology [Ann Oncol] 2017 Sep 01; Vol. 28 (9), pp. 2128-2134.
DOI:	10.1093/annonc/mdx322
Abstrakt:	Background: The phase 3 CAIRO3 study showed that capecitabine plus bevacizumab (CAP-B) maintenance treatment after six cycles capecitabine, oxaliplatin, and bevacizumab (CAPOX-B) in metastatic colorectal cancer (mCRC) patients is effective, without compromising quality of life. In this post hoc analysis with updated follow-up and data regarding sidedness, we defined subgroups according to RAS/BRAF mutation status and mismatch repair (MMR) status, and investigated their influence on treatment efficacy. Patients and Methods: A total of 558 patients with previously untreated mCRC and stable disease or better after six cycles CAPOX-B induction treatment were randomised to either CAP-B maintenance treatment (n = 279) or observation (n = 279). Upon first progression, patients were to receive CAPOX-B reintroduction until second progression (PFS2, primary end point). We centrally assessed RAS/BRAF mutation status and MMR status, or used local results if central assessment was not possible. Intention-to-treat stratified Cox models adjusted for baseline covariables were used to examine whether treatment efficacy was modified by RAS/BRAF mutation status. Results: RAS, BRAF mutations, and MMR deficiency were detected in 240/420 (58%), 36/381 (9%), and 4/279 (1%) patients, respectively. At a median follow-up of 87 months (IQR 69-97), all mutational subgroups showed significant improvement from maintenance treatment for the primary end point PFS2 [RAS/BRAF wild-type: hazard ratio (HR) 0.57 (95% CI 0.39-0.84); RAS-mutant: HR 0.74 (0.55-0.98); V600EBRAF-mutant: HR 0.28 (0.12-0.64)] and secondary end points, except for the RAS-mutant subgroup regarding overall survival. Adjustment for sidedness instead of primary tumour location yielded comparable results. Although right-sided tumours were associated with inferior prognosis, both patients with right- and left-sided tumours showed significant benefit from maintenance treatment. Conclusions: CAP-B maintenance treatment after six cycles CAPOX-B is effective in first-line treatment of mCRC across all mutational subgroups. The benefit of maintenance treatment was most pronounced in patients with RAS/BRAF wild-type and V600EBRAF-mutant tumours. Clinicaltrials.gov Number: NCT00442637. (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu