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: | G.J.M. Creemers, Stefan M. Willems, Eric Strengman, A.M.T. van der Velden, A.J. ten Tije, W. W. J. de Leng, Frans L. G. Erdkamp, C.J.A. Punt, Miangela M. Lacle, B.C. Tanis, Kaitlyn K.H. Goey, F. de Jongh, Sjoerd G. Elias, Miriam Koopman, G J A Offerhaus, H. van Tinteren |
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| Přispěvatelé: | Other departments, CCA - Cancer Treatment and Quality of Life, CCA -Cancer Center Amsterdam, Oncology |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Oncology RAS mutation status Colorectal cancer Observation CAPOX-Bevacizumab Regimen DNA Mismatch Repair Metastatic disease 0302 clinical medicine Antineoplastic Combined Chemotherapy Protocols Neoplasm Metastasis Aged 80 and over Maintenance treatment Brain Neoplasms Hazard ratio Hematology Middle Aged Bevacizumab Treatment Outcome 030220 oncology & carcinogenesis Female BRAF mutation status Colorectal Neoplasms medicine.drug Adult Proto-Oncogene Proteins B-raf medicine.medical_specialty Disease-Free Survival Capecitabine 03 medical and health sciences Neoplastic Syndromes Hereditary Internal medicine medicine Journal Article Humans Aged Intention-to-treat analysis Surrogate endpoint business.industry medicine.disease Oxaliplatin 030104 developmental biology Mutation ras Proteins business |
| Zdroj: | Annals of Oncology, 28(9), 2128. Oxford University Press Annals of oncology, 28(9), 2128-2134. Oxford University Press |
| ISSN: | 0923-7534 |
| DOI: | 10.1093/annonc/mdx322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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