The evidence supporting this protocol is provided by a phase III multicentre international randomised trial (ICON7) involving 1528 patients comparing carboplatin and paclitaxel with the same regimen plus bevacizumab in patients with ovarian cancer.r
Within this group 502 patients were classified as having high risk disease, defined as sub-optimally debulked Stage III or IV disease.
Between December 2006 and February 2009, 764 patients received the standard chemotherapy regimen with carboplatin AUC 5/6 and paclitaxel 175 mg/m2, given every 3 weeks for 6 cycles and 764 patients received the same regimen plus bevacizumab 7.5mg/kg concurrently for 5 or 6 cycles, and continued for an additional 12 cycles or until disease progression.
The primary end point was progression-free survival (PFS) and secondary end points were overall survival (OS), biologic progression-free survival, response to therapy, toxicity and quality of life.
Efficacy
The ICON 7 trial results did not show a clinically meaningful benefit for the addition of bevacizumab to carboplatin and paclitaxel in the total population. The median PFS was 20.3 months with standard therapy, compared to 21.8 with standard therapy and bevacizumab (HR 0.81; p = 0.004).r
A further analysis of the high risk population subset was undertaken, with the final results presented at the European Cancer Congress in 2013.r After a median follow up of 49 months of the high risk population, the median PFS was 10.5 months in the control group versus 16.0 months in the research group (HR=0.73; 95% CI, 0.61 - 0.88; p = 0.0001). In the high risk population the median OS was 30.3 months in the control group versus 39.7 months in the research group (HR=0.78; 95% CI, 0.63 - 0.97; p = 0.03).
Toxicityr
Bevacizumab treatment appeared to be associated with an increase in bleeding, hypertension of grade 2 or higher (18% with bevacizumab vs. 2% with standard therapy), thromboembolic events of grade 3 or higher (7% with bevacizumab vs. 3% with standard therapy), and gastrointestinal perforations (occurring in 10 patients in the bevacizumab group vs. 3 patients in the standard therapy group).
Adverse events (grade 3 or above) |
Standard chemotherapy % |
Bevacizumab % |
Any event |
54 |
65 |
Any bleeding |
<1 |
1 |
Bleeding with CNS |
0 |
<1 |
Abscess with fistula |
1 |
1 |
GI perforation |
<1 |
1 |
Hypertension |
<1 |
6 |
Proteinuria |
<1 |
1 |
Any thrombolic event |
3 |
7 |
Neutropenia |
15 |
17 |
Febrile neutropenia |
2 |
3 |
Thrombocytopenia |
2 |
3 |
Congestive cardiac failure |
<1 |
<1 |
Complication of wound healing |
<1 |
1 |
Hyperbilirubinaemia |
0 |
0 |