Maintenance treatment with capecitabine and bevacizumab versus observation in metastatic colorectal cancer: updated results and molecular subgroup analyses of the phase 3 CAIRO3 studyGoey, K. K. H., Elias, S. G., van Tinteren, H., Laclé, M. M., Willems, S. M., Offerhaus, G. J. A., de Leng, W. W. J., Strengman, E., Ten Tije, A. J., Creemers, G-J. M., van der Velden, A., de Jongh, F. E., Erdkamp, F. L. G., Tanis, B. C., Punt, C. J. A. & Koopman, M., 1-Sep-2017, In : Annals of Oncology. 28, 9, p. 2128-2134 7 p.
Research output: Contribution to journal › Article › Academic › peer-review
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.
|Number of pages||7|
|Journal||Annals of Oncology|
|Publication status||Published - 1-Sep-2017|
- Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Bevacizumab/administration & dosage, Brain Neoplasms/genetics, Capecitabine/administration & dosage, Colorectal Neoplasms/drug therapy, DNA Mismatch Repair/genetics, Disease-Free Survival, Female, Humans, Male, Middle Aged, Mutation, Neoplasm Metastasis, Neoplastic Syndromes, Hereditary/genetics, Observation, Proto-Oncogene Proteins B-raf/genetics, Treatment Outcome, ras Proteins/genetics