Maintenance treatment with capecitabine and bevacizumab in metastatic colorectal cancer (CAIRO3): a phase 3 randomised controlled trial of the Dutch Colorectal Cancer Group

Lieke H. J. Simkens, Harm van Tinteren, Anne May, Albert J. ten Tije, Geert-Jan M. Creemers, Olaf J. L. Loosveld, Felix E. de Jongh, Frans L. G. Erdkamp, Zoran Erjavec, Adelheid M. E. van der Torren, Jolien Tol, Hans J. J. Braun, Peter Nieboer, Jacobus J. M. van der Hoeven, Janny G. Haasjes, Rob L. H. Jansen, Jaap Wals, Annemieke Cats, Veerle A. Derleyn, Aafk E. H. HonkoopLinda Mol, Cornelis J. A. Punt, Miriam Koopman*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

312 Citations (Web of Science)

Abstract

Background The optimum duration of first-line treatment with chemotherapy in combination with bevacizumab in patients with metastatic colorectal cancer is unknown. The CAIRO3 study was designed to determine the efficacy of maintenance treatment with capecitabine plus bevacizumab versus observation. Methods In this open-label, phase 3, randomised controlled trial, we recruited patients in 64 hospitals in the Netherlands. We included patients older than 18 years with previously untreated metastatic colorectal cancer, with stable disease or better after induction treatment with six 3-weekly cycles of capecitabine, oxaliplatin, and bevacizumab (CAPOX-B), WHO performance status of 0 or 1, and adequate bone marrow, liver, and renal function. Patients were randomly assigned (1: 1) to either maintenance treatment with capecitabine and bevacizumab (maintenance group) or observation (observation group). Randomisation was done centrally by minimisation, with stratification according to previous adjuvant chemotherapy, response to induction treatment, WHO performance status, serum lactate dehydrogenase concentration, and treatment centre. Both patients and investigators were aware of treatment assignment. We assessed disease status every 9 weeks. On first progression (defined as PFS1), patients in both groups were to receive the induction regimen of CAPOX-B until second progression (PFS2), which was the study's primary endpoint. All endpoints were calculated from the time of randomisation. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov,number NCT00442637. Findings Between May 30, 2007, and Oct 15, 2012, we randomly assigned 558 patients to either the maintenance group (n=279) or the observation group (n=279). Median follow-up was 48 months (IQR 36-57). The primary endpoint of median PFS2 was significantly improved in patients on maintenance treatment, and was 8.5 months in the observation group and 11.7 months in the maintenance group (HR 0.67, 95% CI 0.56-0.81, p
Original languageEnglish
Pages (from-to)1843-1852
JournalLancet
Volume385
Issue number9980
DOIs
Publication statusPublished - 9 May 2015

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