Single-agent capecitabine as maintenance therapy after induction of XELOX (or FOLFOX) in first-line treatment of metastatic colorectal cancer: randomized clinical trial of efficacy and safety

Background: The optimal strategy of maintenance therapy for patients with mCRC is controversial. This study was to evaluate the efficacy and safety of maintenance therapy with capecitabine versus observation following inductive chemotherapy in patients with metastatic colorectal cancer. In this randomized, open-label, multicenter, phase III trial, patients who received 18-24 weeks of induction chemotherapy with XELOX or FOLFOX and achieved disease control were randomly assigned centrally (1:1) to receive maintenance therapy of capecitabine or only observation until disease progression. The primary end point was progression-free survival (PFS) from randomization; the secondary end points included overall survival (OS), PFS from induction treatment (PFS2) and safety. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02027363. Between 30 July 2010 and 15 September 2013, 274 patients were enrolled in the study from 11 sites in China and randomly assigned to maintenance group (n = 136) or observation group (n = 138). Clinicopathological characteristics were balanced in two groups. The median follow-up time from randomization was 29.0 months [interquartile range (IQR) 21-36 months]. The primary end point of PFS was statistically significantly longer in capecitabine maintenance group than in observation group {6.43 [95% confidence interval (CI) 5.26-7.71] versus 3.43 (2.83-4.16) months, HR 0.54 (0.42-0.70), P < 0.001}. The median OS of capecitabine maintenance group was longer than that of observation group, but not statistically significant [25.63 (22.46-27.80) versus 23.30 (19.68-26.92) months; HR 0.85 (0.64-1.11), P = 0.2247]. Similar safety profiles were observed in both arms. The most common grade 3 or 4 toxicities in capecitabine maintenance group versus observation group were neutropenia, hand-foot syndrome, and mucositis. Maintenance therapy with a single agent of capecitabine can be considered an appropriate option following the induction of XELOX or FOLFOX in mCRC patients with acceptable toxicities. NCT02027363.