Published in:
01-12-2010 | Short communication
Angiogenesis - still a worthwhile target for breast cancer therapy?
Published in: Breast Cancer Research | Special Issue 4/2010
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Tumour angiogenesis was identified as a target for cancer therapy in the 1970s. To date, one anti-angiogenesis treatment, bevacizumab, which targets the vascular endothelial growth factor (VEGF) signalling pathway, has been licensed for the treatment of advanced breast cancer. However, in clinical studies only modest improvements in progression-free survival have been seen for anti-angiogenic treatment of this disease (Table 1). Many patients have no response to these drugs at all, and often after an initial response patients soon relapse. Indeed, the US Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) recently voted almost unanimously to remove the treatment of advanced breast cancer as a licensed indication for bevacizumab. Results from trials in the adjuvant and neoadjuvant setting for breast cancer are still awaited. We discuss why anti-angiogenesis therapies have not lived up to their early expectations and how new strategies for their use may lead to their greater effectiveness.
Table 1
Phase 3 trial results, to date, of anti-angiogenic agents in the treatment of advanced breast cancer
|
Trial name and design
|
Treatment
type
|
Progression free survival (months)a
|
Overall survival (months)a
|
Response ratea
|
|---|---|---|---|---|
|
Capecitabine ± bevacizumab
|
Refractory
|
4.86 versus 4.17
(HR 0.98; P = 0.857)
|
15.1 versus 14.5
|
19.8% versus 9.1%
(P = 0.001)
|
|
RIBBON-2: second line chemotherapy ± bevacizumab
|
Second line
|
7.2 versus 5.1
(HR 0.775; P = 0.0072)
|
18.0 versus 16.4
(P = 0.372)
|
39.5% versus 29.6%
(P = 0.0193)
|
|
E2100: paclitaxel ± bevacizumab
|
First line
|
11.8 versus 5.9
(HR 0.60; P = <0.001)
|
26.7 versus 25.2
(HR 0.88; P = 0.16)
|
36.9% versus 21.2%
(P < 0.001)
|
|
AVADO: docetaxel ± bevacizumab
|
First line
|
8.8 versus 8.0
(HR 0.61; P = 0.0001)
|
Not published
|
44.4% versus 63.1%
(P = 0.0001)
|
|
RIBBON-1: capecitabine (C) or taxane (T) or anthracycline (A) ± bevacizumab or placebo
|
Second line
|
C: 8.6 versus 5.7
(HR 0.688; P = 0.0002)
A + Tb: 9.2 versus 8.0
(HR 0.644; P ≤ 0.0001)
|
C: 29.0 versus 21.2
(HR 0.847; P = 0.2706)
A + Tb: 25.2 versus 23.8
(HR 1.032; P = 0.8298)
|
C: 35.4% versus 23.6%
(P = 0.0097)
A + Tb: 51.3% versus 37.9%
(P = 0.0054)
|
|
Capecitabine ± sunitinib
|
Refractory
|
5.5 versus 5.9
(HR 1.224)
|
16.4 versus 16.5
(HR 0.995)
|
18.6% versus 16.3%
|
|
Capecitabine versus sunitinib
|
Refractory
|
2.8 versus 4.2
(HR 1.473; P < 0.001)
|
Not published
|
9.1% versus 12.9%
|
|
Docetaxel ± sunitinib
|
First line
|
8.6 versus 8.3
(HR 0.922)
|
24.8 versus 25.5
(HR 1.207)
|
51% versus 39%
(P = 0.0018)
|