Introduction
Bevacizumab in metastatic breast cancer
First-line trials
Study |
n
| Line | Therapy | Median PFS | Median OS | ORR | Ref | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
BEV | no BEV | HR |
P
| BEV | no BEV | HR |
P
| BEV | no BEV |
P
| ||||||||
E2100
| 673 | 1st
| Paclitaxel ± BEV 10 mg/kg | 11.8 | vs | 5.9 |
0.6
|
<0.001
| 26.7 | vs | 25.2 |
0.88
| 0.16 | 36.9% | vs | 21.2% |
<0.001
| [7] |
AVADO
| 736 | 1st
| Docetaxel + BEV 7.5 mg/kg vs. docetaxel + BEV 15 mg/kg vs. docetaxel + placebo | 9 10.1 | vs | 8.2 |
0.77
0.67
|
0.045
<0.001
| 30.8 30.2 | vs | 31.9 |
1.05
1.03
| 0.72 0.85 | 55% 64% | vs | 46% |
0.07
<0.001
| [8] |
RIBBON-1
| 615 | 1st
| Capecitabine ± BEV 15 mg/kg | 8.6 | vs | 5.7 |
0.69
|
<0.001
| 29 | vs | 21 |
0.85
| 0.27 | 35.4% | vs | 23.6% |
0.01
| [9] |
RIBBON-1
| 622 | 1st
| Anthracycline or taxane ± BEV 15 mg/kg | 9.2 | vs | 8.0 |
0.64
|
<0.001
| 25.2 | vs | 23.8 |
1.03
| 0.83 | 51.3% | vs | 37.9% |
0.05
| [9] |
AVEREL
b
| 424 | 1st
| Docetaxel + trastuzumab ± BEV 15 mg/kg | 16.5 | vs | 13.7 |
0.82
|
0.078
| >38 | vs | >38 |
1.01
| 0.95 | 74% | vs | 70% | 0.349 | [12] |
MERiDiAN
| 481 | 1st
| Paclitaxel ± BEV 10 mg/kg | 11.0 | vs | 8.8 |
0.68
|
0.0007
| NR | 54% | vs | 33.2% |
<0.001
| [35] | ||||
AVG2119g
| 462 | 2nd–3rd
| Capecitabine ± BEV 15 mg/kg | 4.8 | vs | 4.2 |
0.98
|
0.857
| 15.1 | vs | 14.5 |
NR
| NR | 19.8% | vs | 9.1% |
0.001
| [49] |
RIBBON-2
| 684 | 2nd
| Taxane or gemcitabine or capecitabine or vinorelbine ± BEV 10 or 15 mg/kg | 7.2 | vs | 5.1 |
0.78
|
0.007
| 18.0 | vs | 16.4 |
0.9
| 0.372 | 39.5% | vs | 29.6% | 0.193 | [18] |
TANIA
| 494 | 2nd
(and-3rd) | Taxane, capecitabine, anthracycline, gemcitabine ± BEV 10 or 15 mg/kg | 6.3 | vs | 4.2 |
0.75
|
0.007
| 19.7 | vs | 18.7 |
0.93
| 0.725 | 21% | vs | 17% | 0.35 | |
CALGB 40503
a
| 343 | 1st
| Letrozole ± BEV 15 mg/kg | 20.2 | vs | 15.6 |
0.75
|
0.016
| 47.2 | vs | 43.9 |
0.87
| 0.188 | 69% | vs | 49% |
0.04
| [16] |
LEA
a
| 374 | 1st
| Letrozole or fulvestrant ± BEV 15 mg/kg | 19.3 | vs | 14.4 |
0.83
|
0.126
| 52.1 | vs | 51.8 |
0.87
| 0.518 | 41% | vs | 22% |
<0.001
| [17] |
Second-line trials
Maintenance therapy
Bevacizumab in early and locally advanced operable breast cancer
Neoadjuvant trials
Study |
n
| Phase | Subtype | Therapy | pCR rate | 3-year DFS | 3-year OS | Ref | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
BEV (%) | No BEV (%) |
P
| BEV | No BEV | HR |
P
| BEV | No BEV | HR |
P
| ||||||
GeparQuinto
| 678 | III | TNBC | EC → T ± BEV 15 mg/kg | 39 | 28 |
0.004
| 80.8% | 80.8% |
1.03
| 0.784 | 89.7% | 89.7% |
0.974
| 0.842 | |
NSABP B40
| 1206 | III | HER2− | TX → AC or T + gemcitabine → AC ± BEV 15 mg/kg neoadjuvant and adjuvant | 35 | 28 |
0.02
| NR | NR |
0.8
| 0.06 | NR | NR |
0.65
|
0.004
| |
ARTemis
| 800 | III | HER2− | T → FEC ± BEV 15 mg/kg | 22 | 17 |
0.03
| 74% | 78% |
1.18
| 0.25 | 81% | 85% |
1.26
| 0.19 |
Adjuvant trials
Study |
n
| Subtype | Chemotherapy | Primary Endpoint | DFS | OS | Ref | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
BEV | No BEV | HR |
P
| BEV | No BEV | HR |
P
| ||||||
BEATRICE
| 2591 | TNBC | Anthracycline and/or taxane ± BEV 5 mg/kg/week | PFS | 5y 80% | 5y 77% |
0.87
| 0.18 | 5y 88% | 5y 88% |
0.93
| 0.52 | |
E5103
| 4994 | HER2− | AC → paclitaxel ± BEV 15 mg/kg ± BEV-Maintenance | PFS | 5y 80% | 5y 77% |
0.87
| 0.17 | NR | NR |
0.89
| 0.41 | [32] |
NSABP B40
| 1206 | HER2− | TX → AC or T + gemcitabine → AC ± BEV 15 mg/kg neoadjuvant and adjuvant | pCR | NR | NR |
0.8
| 0.06 | NG | NG |
0.65
|
0.004
| |
NSABP B44 BETH*
| 3509 | HER2+ | C + T + H ± BEV → H ± BEV T + H ± BEV → FEC → H ± BEV 15 mg/kg | PFS | 3y 92% | 3y 92% |
0.99
| 0.96 | 3y 97% | 3y 96% |
0.87
| 0.44 | [33] |
Toxicity
Grade 3/4 adverse event | BEV (%) (n = 1679) | No BEV (%) (n = 982) |
---|---|---|
Neutropenia
|
10.0
|
7.1
|
Sensory neuropathy | 9.5 | 8.5 |
Hypertension
|
9.0
|
1.2
|
Febrile neutropenia
|
6.5
a
|
3.5
|
Venous thromboembolic event | 2.8 | 3.8 |
Proteinuria
|
2.3
|
0.0
|
Arterial thromboembolic event | 1.6 | 0.3 |
Bleeding | 1.5 | 0.4 |
Left ventricular systolic function | 1.5 | 0.2 |
Wound dehiscence | 0.8 | 0.3 |
Fistula | 0.5 | 0.3 |
GI perforation | 0.5 | 0.3 |
RPLS | <0.1 | 0.0 |