| advanced breast cancer (metastatic) | All results are NS for efficacy inferior to taxanes in terms of adverse events grade 3 in RIBBON-I (Robert) on top capecitabine, 2009 inferior to taxanes in terms of hypertension (grade 3) in RIBBON-I (Robert) on top capecitabine, 2009 inferior to taxanes in terms of adverse events grade 3 in RIBBON-I (Robert) on top Tax or anthra, 2009 inferior to taxanes in terms of serious adverse events in RIBBON-I (Robert) on top Tax or anthra, 2009 inferior to taxanes in terms of hypertension (grade 3) in RIBBON-I (Robert) on top Tax or anthra, 2009 inferior to taxanes in terms of permanent discontinuation in RIBBON-I (Robert) on top Tax or anthra, 2009 | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| E2100 (Miller), 2007 | vs taxanes | progression-free survival (PFS) 0.56 [0.32; 0.97] objective response 2.20 [1.68; 2.88] | | proteinuria (grade 3) ∞ [NaN; ∞] left ventricular systolic dysfunction (grade 2 or 3) 2.84 [0.30; 27.21] overall survival (OS) 0.86 [0.49; 1.52] hypertension (grade 3) ∞ [NaN; ∞] arterial/venous thromboembolism (grade 3) 1.52 [0.50; 4.59] gastrointestinal perforation (grade 3) ∞ [NaN; ∞] bleeding (grade 3) ∞ [NaN; ∞] high-grade congestive heart failure 7.58 [0.95; 60.32] permanent discontinuation 1.14 [0.86; 1.52] treatment-related deaths 1.90 [0.17; 20.82] | | AVADO (Miles) 15mg , 2009 | vs taxanes | progression-free survival (PFS) 0.69 [0.54; 0.88] objective response 1.22 [1.10; 1.36] | | overall survival (OS) 0.92 [0.62; 1.37] | | RIBBON-I (Robert) on top capecitabine, 2009 | vs taxanes | objective response 1.50 [1.09; 2.05] | adverse events grade 3 1.62 [1.21; 2.17] hypertension (grade 3) 10.20 [2.49; 41.74] | venous thromboembolic event (grade 3) 1.42 [0.61; 3.31] arterial thromboembolic event 1.00 [0.25; 3.94] proteinuria (grade 3) ∞ [NaN; ∞] left ventricular systolic dysfunction (grade 2 or 3) 2.99 [0.36; 24.63] overall survival (OS) 0.85 [0.40; 1.82] progression-free survival (PFS) 0.68 [0.34; 1.34] serious adverse events 1.28 [0.92; 1.79] gastrointestinal perforation (grade 3) NaN [NaN; NaN] bleeding (grade 3) 0.50 [0.03; 7.91] high-grade congestive heart failure 6.91 [0.91; 52.33] permanent discontinuation 1.00 [0.63; 1.58] treatment-related deaths 0.60 [0.18; 1.93] | | RIBBON-I (Robert) on top Tax or anthra, 2009 | vs taxanes | objective response 1.36 [1.09; 1.68] | adverse events grade 3 1.70 [1.32; 2.19] serious adverse events 1.49 [1.10; 2.01] hypertension (grade 3) 9.78 [2.39; 40.07] permanent discontinuation 3.22 [1.80; 5.77] | venous thromboembolic event (grade 3) 0.82 [0.30; 2.21] arterial thromboembolic event 1.96 [0.22; 17.39] proteinuria (grade 3) ∞ [NaN; ∞] left ventricular systolic dysfunction (grade 2 or 3) 1.47 [0.59; 3.64] overall survival (OS) 1.03 [0.48; 2.20] progression-free survival (PFS) 0.77 [0.38; 1.56] gastrointestinal perforation (grade 3) 2.45 [0.29; 20.80] bleeding (grade 3) ∞ [NaN; ∞] treatment-related deaths 0.65 [0.23; 1.85] | | AVF2119g (Miller) cape, 2005 | vs taxanes | objective response 2.17 [1.34; 3.52] | | pulmonary embolism (grade 3) 0.94 [0.19; 4.60] overall survival (OS) 1.07 [0.54; 2.11] progression-free survival (PFS) 0.98 [0.49; 1.96] cardiomyopathy (grade 3) 1.88 [0.17; 20.56] high-grade congestive heart failure 2.52 [0.53; 12.00] | | Burstein, 2005 | vs taxanes | | | objective response 3.09 [0.75; 12.74] arterial/venous thromboembolism (grade 3) ∞ [NaN; ∞] | | RIBBON-2 (Brufsky), 2009 | vs taxanes | objective response 1.33 [1.03; 1.73] | | overall survival (OS) 0.90 [0.46; 1.77] progression-free survival (PFS) 0.78 [0.43; 1.43] high-grade congestive heart failure ∞ [NaN; ∞] | | AVADO (Miles) 7.5mg, 2010 | vs taxanes | | | overall survival (OS) 1.05 [0.81; 1.36] progression-free survival (PFS) 0.86 [0.72; 1.03] | | Martin bevacizumab, 2011 | vs taxanes | | | left ventricular systolic dysfunction (grade 2 or 3) NaN [NaN; NaN] progression-free survival (PFS) 0.79 [0.33; 1.90] objective response 1.24 [0.91; 1.69] serious adverse events 0.75 [0.46; 1.23] hypertension (grade 3) 6.49 [0.81; 51.71] permanent discontinuation 1.70 [0.89; 3.23] treatment-related deaths 0.31 [0.03; 2.92] |
| Trial | Treatments | Patients | Method |
|---|
| E2100 (Miller), 2007 | paclitaxel + bevacizumab 10 mg/kg iv every 2 weeks (n=368) vs. paclitaxel 90 mg per square meter of body-surface area on days 1, 8, and 15 every 4 weeks (n=354) | patients with metastatic breast cancer not previously treated | open Parallel groups Sample size: 368/354 Primary endpoint: PFS FU duration: | | AVADO (Miles) 15mg , 2009 | Docetaxel + bevacizumab 7.5 mg/kg iv every 3 weeks (n=-9) vs. (n=-9) | first-line treatment of HER2-negative metastatic breast cancer | Sample size: -9/-9 Primary endpoint: PFS FU duration: | | RIBBON-I (Robert) on top capecitabine, 2009 | Capecitabine + bevacizumab 15 mg/kg iv every 3 weeks (n=-9) vs. capecitabine (Cape; 2,000 mg/m(2) for 14 days), (n=-9) | irst-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer | double-blind Sample size: -9/-9 Primary endpoint: PFS FU duration: | | RIBBON-I (Robert) on top Tax or anthra, 2009 | Taxanes or anthracyclines + bevacizumab 15 mg/kg iv every 3 weeks (n=-9) vs. taxane (Tax) -based (nab-paclitaxel 260 mg/m(2), docetaxel 75 or 100 mg/m(2)), or anthracycline (Anthra) -based (doxorubicin or epirubicin combinations [doxorubicin/cyclophosphamide, epirubicin/cyclophosphamide, fluorouracil/epirubicin/cyclophosphamide, o (n=-9) | irst-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer | Sample size: -9/-9 Primary endpoint: PFS FU duration: | | AVF2119g (Miller) cape, 2005 | capecitabine + bevacizumab 15 mg/kg iv every 3 weeks (n=232) vs. capecitabine (2,500 mg/m2/d) twice daily on day 1 through 14 every 3 weeks (n=230) | patients with metastatic breast cancer previously treated with an anthracycline and a taxane | open Parallel groups Sample size: 232/230 Primary endpoint: PFS FU duration: | | Burstein, 2005 | Methotrexate + cyclophosphamide + bevacizumab 10 mg/kg iv every 2 weeks (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: response FU duration: | | RIBBON-2 (Brufsky), 2009 | addition of BV to chemotherapies used as second-line treatment for MBC (n=-9) vs. chemo+placebo (n=-9) | second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer | open Parallel groups Sample size: -9/-9 Primary endpoint: investigator-assessed PFS FU duration: | | AVADO (Miles) 7.5mg, 2010 | bevacizumab 7.5mg/kg every 3 weeks plus docetaxel (n=248) vs. placebo plus docetaxel (n=241)
| first-line treatment of HER2-negative metastatic breast cancer
| double-blind Sample size: 248/241 Primary endpoint: PFS FU duration:
| | Martin bevacizumab, 2011 | bevacizumab 10 mg/kg intravenously on days 1 and 15 of each 28-day cycle (n=-9) vs. control (n=-9) | patients with HER2-negative locally recurrent or metastatic breast cancer | open design Sample size: -9/-9 Primary endpoint: FU duration: |
|
| lung cancer (metastatic) | All results are NS for efficacy | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| vs | | | | | vs | | | | | vs | | | | | vs | | | | | vs | | | | | vs | | | |
| Trial | Treatments | Patients | Method |
|---|
| Reck, 2010 | GP+bev (n=-9) vs. GP (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | Sandler, 2006 | PCp +bev (n=-9) vs. PCp (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | Johnson, 2004 | PCp +bev (n=-9) vs. PCp (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | Nishio, 2009 | PCp +bev (n=-9) vs. PCp (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | Herbst, 2007 | D/M +bev (n=-9) vs. D/M (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | Herbst, 2011 | erl+bev (n=-9) vs. erl (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: |
|
| renal-cell carcinoma (advanced) | All results are NS for efficacy | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| CALGB 90206, 2010 | vs interferon alpha | PFS 0.71 [0.61; 0.83] | | OS 0.86 [0.73; 1.01] | | AVOREN, 2007 | vs interferon alpha | PFS 0.63 [0.52; 0.76] | | OS 0.86 [0.72; 1.03] | | Yang, 2003 | vs interferon alpha | | | |
| Trial | Treatments | Patients | Method |
|---|
| CALGB 90206, 2010 | bevacizumab (10 mg/kg intravenously every 2 weeks) plus IFN- (9 million units subcutaneously
three times weekly) (n=369) vs. same dose and schedule of IFN- monotherapy (n=363) | Patients with previously untreated, metastatic clear cell RCC | Parallel groups Sample size: 369/363 Primary endpoint: OS FU duration: | | AVOREN, 2007 | bevacizumab (10 mg/kg every 2 weeks) plus IFN (9 MIU subcutaneously three times a week) (n=327) vs. IFN plus placebo (n=322) | patients with previously untreated mRCC | Sample size: 327/322 Primary endpoint: FU duration: | | Yang, 2003 | bevacizumab at doses of 3 and 10 mg per kilogram of body weight, given every two weeks (n=76) vs. placebo (n=40) | patients with metastatic renal-cell carcinoma | Parallel groups Sample size: 76/40 Primary endpoint: FU duration: |
|
