angiogenesis inhibitors

Description Results NMA

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]

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]

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]

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]

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]

objective response 3.09 [0.75; 12.74]

arterial/venous thromboembolism (grade 3) ∞ [NaN; ∞]

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; ∞]

overall survival (OS) 1.05 [0.81; 1.36]

progression-free survival (PFS) 0.86 [0.72; 1.03]

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]

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)

open

Parallel groups

Sample size: 368/354

Primary endpoint: PFS

FU duration:

Docetaxel + bevacizumab 7.5 mg/kg iv every 3 weeks (n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint: PFS

FU duration:

Capecitabine + bevacizumab 15 mg/kg iv every 3 weeks (n=-9)

vs.

capecitabine (Cape; 2,000 mg/m(2) for 14 days), (n=-9)

double-blind

Sample size: -9/-9

Primary endpoint: PFS

FU duration:

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)

Sample size: -9/-9

Primary endpoint: PFS

FU duration:

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)

open

Parallel groups

Sample size: 232/230

Primary endpoint: PFS

FU duration:

Methotrexate + cyclophosphamide + bevacizumab 10 mg/kg iv every 2 weeks (n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint: response

FU duration:

addition of BV to chemotherapies used as second-line treatment for MBC (n=-9)

vs.

chemo+placebo (n=-9)

open

Parallel groups

Sample size: -9/-9

Primary endpoint: investigator-assessed PFS

FU duration:

bevacizumab 7.5mg/kg every 3 weeks plus docetaxel (n=248)

vs.

placebo plus docetaxel (n=241)

double-blind

Sample size: 248/241

Primary endpoint: PFS

FU duration:

bevacizumab 10 mg/kg intravenously on days 1 and 15 of each 28-day cycle (n=-9)

vs.

control (n=-9)

open design

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

motesanib 125 mg orally once per da (n=91)

vs.

placebo (n=94)

double-blind

Sample size: 91/94

Primary endpoint:

FU duration:

PFS 0.64 [0.44; 0.93]

OS 1.01 [0.71; 1.44]

sorafenib (400 mg, twice daily) (n=-9)

vs.

placebo (n=-9)

double-blind

Parallel groups

Sample size: -9/-9

Primary endpoint:

FU duration:

OS 1.02 [0.71; 1.46]

PFS 0.79 [0.56; 1.11]

paclitaxel (90mg/m(2), weekly, intravenously, 3 weeks on/1 week off) plus sorafenib (400mg, orally, twice daily) (n=-9)

vs.

paclitaxel (90mg/m(2), weekly, intravenously, 3 weeks on/1 week off) (n=-9)

double-blind

Parallel groups

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=456)

vs.

(n=457)

double-blind

Sample size: 456/457

Primary endpoint: overall survival (OS).

FU duration:

phase III

GP+bev (n=-9)

vs.

GP (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

PCp +bev (n=-9)

vs.

PCp (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

PCp +bev (n=-9)

vs.

PCp (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

PCp +bev (n=-9)

vs.

PCp (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

D/M +bev (n=-9)

vs.

D/M (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

erl+bev (n=-9)

vs.

erl (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

cediranib 20mg daily to carboplatin/paclitaxel (n=-9)

vs.

(n=-9)

double-blind

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

phase II

(n=-9)

vs.

(n=-9)

double-blind

Sample size: -9/-9

Primary endpoint:

FU duration:

phase II/III

(n=-9)

vs.

(n=-9)

double-blind

Sample size: -9/-9

Primary endpoint: Overall Survival

FU duration:

carboplatin (area under the curve, 6 mg/ml · min) and paclitaxel (200 mg/m(2)) intravenously for up to six 3-week cycles plus either motesanib 125 mg (n=-9)

vs.

(n=-9)

double-blind

Sample size: -9/-9

Primary endpoint: OS

FU duration:

phase III

pazopanib in combination with pemetrexed (n=-9)

vs.

(n=-9)

open-label

Sample size: -9/-9

Primary endpoint: progression-free survival (PFS).

FU duration:

phase II

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

phase-II

daily sorafenib (400 mg twice a day) or matching placebo plus gemcitabine (1,250 mg/m(2) per day on days 1 and 8) and cisplatin (75 mg/m(2) on day 1) for up to six 21-day cycles (n=385)

vs.

gemcitabine/cisplatin alone (n=-9387)

Sample size: 385/-9387

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

phase II

up to six 21-day cycles of carboplatin area under the curve 6 and paclitaxel 200 mg/m(2) (CP) on day 1, followed by sorafenib 400 mg twice a day on days 2 to 19 (n=464)

vs.

(n=462)

Sample size: 464/462

Primary endpoint:

FU duration:

phase III

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

sunitinib 37.5 mg/day plus erlotinib 150 mg/day continuously in 4-week cycles (n=-9)

vs.

placebo plus erlotinib (n=-9)

double-blind

Sample size: -9/-9

Primary endpoint:

FU duration:

phase II phase II

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint: OS

FU duration:

phase III

vandetanib or placebo as maintenance (n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

phase 2

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint: progression-free survival (PFS) rate at 3 months

FU duration:

phase II

vandetanib 300 mg/d (n=617)

vs.

placebo (n=307)

Sample size: 617/307

Primary endpoint: overall survival

FU duration:

once-daily vandetanib 300 mg (n=83)

vs.

gefitinib 250 mg (n=85)

double-blind

Sample size: 83/85

Primary endpoint:

FU duration:

phase ii

vandetanib 100 mg/d plus pemetrexed 500 mg/m(2) every 21 days (n=256)

vs.

placebo plus pemetrexed (n=278)

double-blind

Sample size: 256/278

Primary endpoint: Progression-free survival (PFS)

FU duration:

(n=-9)

vs.

(n=-9)

double-blind

Sample size: -9/-9

Primary endpoint:

FU duration:

phase ii

vandetanib (100 or 300 mg/d) plus docetaxel (75 mg/m2 intravenous infusion every 21 days) (n=-9)

vs.

placebo plus docetaxel (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

phase II

PFS 0.71 [0.61; 0.83]

OS 0.86 [0.73; 1.01]

PFS 0.63 [0.52; 0.76]

OS 0.86 [0.72; 1.03]

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)

Parallel groups

Sample size: 369/363

Primary endpoint: OS

FU duration:

bevacizumab (10 mg/kg every 2 weeks) plus IFN (9 MIU subcutaneously three times a week) (n=327)

vs.

IFN plus placebo (n=322)

Sample size: 327/322

Primary endpoint:

FU duration:

bevacizumab at doses of 3 and 10 mg per kilogram of body weight, given every two weeks (n=76)

vs.

placebo (n=40)

Parallel groups

Sample size: 76/40

Primary endpoint:

FU duration: