Maintenance treatment with capecitabine and bevacizumab versus observation after induction treatment with chemotherapy and bevacizumab in metastatic colorectal cancer (mCRC): The phase III CAIRO3 study of the Dutch Colorectal Cancer Group (DCCG).

Abstract

3502 Background: The optimal duration of chemotherapy and bevacizumab in mCRC is not well established. The CAIRO3 study investigated the efficacy of maintenance treatment with capecitabine plus bevacizumab versus observation in mCRC pts not progressing during induction treatment with capecitabine, oxaliplatin and bevacizumab (CAPOX-B). Methods: Previously untreated mCRC pts, PS 0-1, with stable disease or better after 6 cycles of CAPOX-B, not eligible for metastasectomy and eligible for future treatment with oxaliplatin, were randomized between observation (arm A) or maintenance treatment with capecitabine 625 mg/m2 bid dailycontinuouslyand bevacizumab 7.5 mg/kg iv q 3 weeks (arm B). Upon first progression (PFS1), pts in both arms were treated with CAPOX-B until second progression (PFS2, primary endpoint). For pts not able to receive CAPOX-B upon PFS1, PFS2 was considered equal to PFS1. Secondary endpoints were overall survival (OS) and time to second progression (TTP2), which was defined as the time to progression or death on any treatment following PFS1. All endpoints were calculated from the time of randomization. Results: A total of 558 pts were randomized. Median follow-up is 33 months. The median number of maintenance cycles in arm B was 9 (range 1-54). The median PFS1 in arm A vs B was 4.1 vs 7.4 months (HR 0.44, 95% CI 0.37-0.54, p<0.0001). Upon PFS1, 72% of pts received CAPOX-B in arm A and 44% in arm B. The median PFS2 was 10.4 vs 10.4 months (HR 0.86, 95% CI 0.7-1.04, p=0.12). The median TTP2 in arm A vs B was 11.5 vs 15.4 months (HR 0.58, 95% CI 0.48-0.72, p<0.0001), and the median OS was 17.9 vs 21.7 months (HR 0.77, 95% CI 0.62-0.96, p=0.02), respectively. Conclusions: Maintenance treatment with capecitabine plus bevacizumab after 6 cycles CAPOX-B did not significantly prolong PFS2, which may be due to the lower number of pts in arm B that received CAPOX-B following PFS1. Maintenance treatment significantly prolonged PFS1, TTP2 and OS. Our data support the use of bevacizumab plus capecitabine until progression or unacceptable toxicity. Updated results will be presented. Clinical trial information: NCT00442637.