For this open-label, randomised phase 3 trial, patients aged 70 years and older with previously untreated, unresectable, metastatic colorectal cancer, who were not deemed to be candidates for oxaliplatin-based or irinotecan-based chemotherapy regimens, were randomly assigned in a 1:1 ratio via an interactive voice-response system, stratified by performance status and geographical region. Treatment consisted of capecitabine (1000 mg/m2 orally twice a day on days 1-14) alone or with bevacizumab (7¡¤5 mg/kg intravenously on day 1), given every 3 weeks until disease progression, unacceptable toxic effects, or withdrawal of consent. Efficacy analyses were based on the intention-to-treat population. The primary endpoint was progression-free survival. The trial is registered with , number .
From July 9, 2007, to Dec 14, 2010, 280 patients with a median age of 76 years (range 70-87) were recruited from 40 sites across ten countries. Patients were randomly assigned to receive either bevacizumab plus capecitabine (n=140) or capecitabine only (n=140). Progression-free survival was significantly longer with bevacizumab and capecitabine than with capecitabine alone (median 9¡¤1 months [95 % CI 7¡¤3-11¡¤4] vs 5¡¤1 months [4¡¤2-6¡¤3]; hazard ratio 0¡¤53 [0¡¤41-0¡¤69]; p<0¡¤0001). Treatment-related adverse events of grade 3 or worse occurred in 53 (40 % ) patients in the combination group and 30 (22 % ) in the capecitabine group, and treatment-related serious adverse events in 19 (14 % ) and 11 (8 % ) patients. The most common grade 3 or worse adverse events of special interest for bevacizumab or chemotherapy were hand-foot syndrome (21 [16 % ] vs nine [7 % ]), diarrhoea (nine [7 % ] vs nine [7 % ]), and venous thromboembolic events (11 [8 % ] vs six [4 % ]). Treatment-related deaths occurred in five patients in the combination group and four in the capecitabine group. The most common any-grade adverse event of special interest for bevacizumab was haemorrhage (34 [25 % ] vs nine [7 % ]).
The combination of bevacizumab and capecitabine is an effective and well-tolerated regimen for elderly patients with metastatic colorectal cancer.
F Hoffmann-La Roche.