Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX) an open-label, randomised phase 3 trial

SUMMARY: The authors in this randomized phase III trial specifically enrolled chemo naïve patients, 70 years of age or older, with metastatic ColoRectal Cancer (CRC) because, this sub group of patients are often excluded or under- represented in clinical trials. Two hundred and eighty (N=280) chemo naïve patients with metastatic CRC, deemed not to be candidates for more aggressive regimens such as ELOXATIN® (Oxaliplatin) or CAMPTOSAR® (Irinotecan) based chemotherapy regimens, were randomly assigned in a 1:1 ratio to receive either AVASTIN® (Bevacizumab) plus XELODA® (Capecitabine) (n=140) or XELODA® alone (n=140). Treatment consisted of XELODA® 1000 mg/m2 orally twice a day on days 1—14 alone or with AVASTIN® 7•5 mg/kg, given intravenously on day 1. Treatment was given every 3 weeks until disease progression or until unacceptable toxicities were noted. The median age was 76 years and patients were stratified by performance status. The median number of cycles for AVASTIN® plus XELODA® was 9 and for XELODA® alone was 6 cycles. The primary endpoint was Progression Free Survival (PFS). The PFS was significantly longer with the combination of AVASTIN® and XELODA® versus XELODA® alone (9•1 months vs 5•1 months; Hazard Ratio= 0•53; P<0•0001). The combination treatment in general was well tolerated but with a slightly higher incidence of hand-foot syndrome and hemorrhage compared to single agent XELODA®. Overall Survival (OS) was not significantly different between the treatment groups as this study was not powered to detect OS differences. The authors concluded that, in this study, which only enrolled elderly patients with metastatic CRC, unsuitable for aggressive therapy, a combination of AVASTIN® and XELODA® is a reasonable option with proven benefit. Cunningham D, Lang I, Marcuello E, et al. Lancet Oncol 2013;14:1077-1085