Table 2 Phase III clinical studies incorporating bevacizumab to chemotherapy in breast cancer patients
From: Present and future evolution of advanced breast cancer therapy
Trial and reference | Number of patients | Patient population | Bevacizumab dose | Combination therapy | End point | Benefit in anti-VEGF therapy | Study primary results |
|---|---|---|---|---|---|---|---|
AVF2119[97] | 462 | Pretreated MBC | 15 mg/kg every 3 weeks | Cap 2,500 mg/ m2/day from days 1 to 14 | PFS | No | Bev and Cap significantly increased the ORR compared with single-agent Cap (9.1% vs. 19.8%, P = 0.001), but not PFS (4.2 vs. 4.0 months; HR, 0.98). No significant differences were found in incidence of diarrhea, hand-foot syndrome, and serious bleeding episodes between treatment groups |
ECOG 2100 [98] | 722 | First-line MBC | 10 mg/kg every 2 weeks | P 90 mg/m2 days 1,8,15 | PFS | Yes | Bev and P significantly prolonged PFS compared with P alone (median, 11.8 vs. 5.9 months; HR for progression 0.60, P <0.001) and increased ORR (36.9% vs. 21.2%). No differences in OS between two groups (median 26.7 vs. 25.5 months; HR 0.88, P = 0.16). Adverse effects: grade 3 or 4 hypertension (14.8% vs. 0%, P <0.001), proteinuria (3.6% vs. 0%, P <0.001), headache (2.2% vs. 0%, P = 0.008) and cerebrovascular ischemia (1.9% vs. 0%, P = 0.02) were more common in patients receiving combination treatment |
AVADO [99] | 736 | First-line MBC | 7.5 mg/kg every 3 weeks | D 100 mg/m2 every 3 weeks | PFS | Yes | In stratified analysis, patients receiving Bev had significantly longer PFS compared with the D monotherapy group (Bev at 7.5 mg/kg: me-dian PFS 8.7 vs. 8.0 months, HR 0.79, P = 0.0318; Bev at 15 mg/kg: median PFS 8.8 vs. 8.0 months, HR 0.72, P = 0.0099). ORR improved with the addition of Bev (Bev 7.5 mg/kg: 55% vs. 44%, P = 0.0295; Bev 15 mg/kg: 63% vs. 44%, P = 0.0001). The study was not powered to find differences in OS |
15 mg/kg every 3 weeks | |||||||
RIBBON-1 [101] | 1,237a | First-line MBC | 15 mg/kg every 3 weeks | Cap, taxanes (Nab-Pac and D), anthracycline | PFS | Yes | The median follow-up was 15.6 months in the Cap cohort and 19.2 months in the taxanes and anthracycline cohort. The addition of Bev to Cap, taxanes, or anthracycline-based chemotherapy resulted in statistically significant improvement in PFS |
RIBBON-2 [102] | 684 | Second-line MBC | 15 mg/kg every 3 weeks | Cap, taxanes (Nab-Pac and D), anthracycline, Cap, gemcitabine, vinorelbine | PFS | Yes | Median PFS with Bev was 7.2 vs. 5.1 months (HR 0.78, P = 0.0072). A trend for higher objective response rate with Bev 39.5% vs. 29.6%; P = 0.013, not significant at prespecified 0.01. No difference in OS with combination therapy compared with chemotherapy alone (18 vs. 16.4 months; HR 0.90, P = 0.3741). Among the different chemotherapy regimens used in the trial, taxanes and Cap appeared to be more effective, whereas gemcitabine and vinorelbine appeared less effective |
MO19391 [103] | 2.027a | HER2- MBC or HER2+ if previous Tz | 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks | Taxane-based chemotherapy | Safety | Yes | Median follow-up was 7.4 months. ~75% of patients received taxanes, and 25% were treated with nontaxane regimens (Cap and vinorelbine). Safety and efficacy of Bev plus D or P was similar to results of the E2100 and AVADO trials |