The final analysis of the international phase III QUASAR2 trial confirmed the lack of benefit for bevacizumab (Avastin) as part of the adjuvant treatment of colorectal cancer. “There is no role for bevacizumab in combination with capecitabine as adjuvant treatment for colorectal cancer,” said Rachel Kerr, MBChB, PhD, Associate Professor of Gastrointestinal Oncology at the University of Oxford in the United Kingdom, who presented the data at the European Society for Medical Oncology (ESMO) 2014 Congress.¹ “This is not the happy ending we were hoping for in terms of bevacizumab as adjuvant treatment.”

QUASAR randomly assigned 1,941 stage III and high-risk stage II colorectal cancer patients, postresection, to 8 cycles (24 weeks) of capecitabine or to capecitabine plus bevacizumab (7.5 mg/kg) for 16 cycles (48 weeks). At 3 years, the disease-free survival rate was 78.4% with capecitabine alone and 75.4% with capecitabine/bevacizu­mab (P = .5), and overall survival was 89.4% vs 87.5% (P = .3), respectively, Dr. Kerr announced.

Prognostic Indicators

“Studies have shown that a high tumor-stroma ratio in colorectal cancer predicts for worse prognosis, and we postulated that this subset of patients may specifically benefit from therapy with bevacizumab. Although we were able to confirm a prognostic effect of tumor-stroma ratio, there was no evidence that this marker determined responsiveness to bevacizumab. In fact, subgroup analysis did not reveal a specific subpopulation that benefited,” she said.

Microsatellite instability status was not associated with differences in disease-free survival overall (P = .14); however, a greater treatment effect was seen in the microsatellite-stable group.

“The results suggested that [microsatellite-stable] patients suffer a reduced disease-free survival when bevacizumab is added to single-agent capecitabine (hazard ratio = 1.43, P = .005),” Dr. Kerr indicated.

The combination was associated with significantly more hypertension, proteinuria, and poor wound healing. “An excess of ‘possibly treatment-related’ deaths was found in patients receiving bevacizumab (1.9% vs 0.9%, relative risk = 2.3), and this just reached significance (P = .05),” she added. ■

Disclosure: Dr. Kerr reported no potential conflicts of interest.

Reference

1. Midgley RS, Love S, Tomlinson I, et al: Final results from QUASAR2, a multicenter, international randomized phase III trial of capecitabine +/- bevacizumab in the adjuvant setting of stage II/III colorectal cancer. ESMO 2014 Congress. Abstract LBA12. Presented September 27, 2014.