CAIRO3 Supports Capecitabine, Bevacizumab Maintenance Therapy in Metastatic CRC

A phase III trial reports a significant progression-free survival benefit for capecitabine plus bevacizumab maintenance compared with observation in metastatic colorectal cancer patients

medwireNews: Compared with observation, maintenance therapy with capecitabine and bevacizumab significantly improves progression-free survival in patients with metastatic colorectal cancer (CRC), Dutch researchers report.

This improvement is not at the expense of quality of life, note Miriam Koopman, from University Medical Center Utrecht, and co-authors in The Lancet.

In the phase III CAIRO3 trial, 557 patients with previously untreated metastatic CRC who responded (stable disease or better) to induction treatment with six cycles of capecitabine, oxaliplatin and bevacizumab (CAPOX-B) were randomly assigned to either receive maintenance treatment with capecitabine and bevacizumab or undergo observation.

Patients with disease progression during capecitabine plus bevacizumab or during observation were again treated with CAPOX-B where possible until further progression, with the respective survival endpoints defined as progression-free survival 1 (PFS1) and PFS2.

After a median follow-up of 48 months, median PFS2, which was the primary endpoint, was 11.7 months for the 278 patients in the maintenance therapy group and 8.5 months for the 279 participants of the observation group, a statistically significant difference.

Maintenance therapy also significantly improved PFS1 compared with observation alone, at a median of 8.5 versus 4.1 months. This was also the case for median time to second progression on any treatment given after first progression, at 13.5 and 11.1 months, respectively.

Median overall survival was 21.6 months and 18.1 months in the maintenance and observation groups, respectively, but this difference was not significant.

Patients receiving maintenance treatment had a significantly higher incidence of grade 3 or 4 adverse events than those in the observation arm (60 vs 34%), with grade 3 hand–foot syndrome in particular occurring in significantly more patients in the maintenance than in the observation group (23 vs 0%).

But using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire, the researchers found no deterioration in either global quality of life or the functioning and symptoms subscales for participants receiving maintenance therapy.

They conclude: “Maintenance treatment with capecitabine and bevacizumab should be deemed the preferred strategy in patients with metastatic colorectal cancer with stable disease or better after initial treatment with combination chemotherapy and bevacizumab.”

In a linked commentary, Joleen Hubbard and Axel Grothey, from Mayo Clinic Rochester in Minnesota, USA, say that CAIRO3 provides “the best evidence so far” for maintenance treatment in this setting.

However, they add: “It does not set the one and only standard of care in the management of this disease, but provides very valuable guidance for how to optimise a treatment approach in clinical practice when a regimen of bevacizumab, fluoropyrimidine, and oxaliplatin is used as first-line therapy.”


Simkens LHJ, van Tinteren H, May A, et al. Maintenance treatment with capecitabine and bevacizumab in metastatic colorectal cancer (CAIRO3): a phase 3 randomised controlled trial of the Dutch Colorectal Cancer Group.Lancet; Advance online publication 7 April 2015. doi:10.1016/S0140-6736(14)62004-3

Hubbard JM, Grothey A. When less is more: maintenance therapy in colorectal cancer.Lancet; Advance online publication 7 April 2015. doi:10.1016/S0140-6736(14)62350-3

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