Avastin Flashcards
In which settings is Bev licenced?
First-line = In combo with carboplatin and paclitaxel for the front-line treatment of adults with advanced (FIGO Stages IIIB, IIIC and IV) epithelial ovarian, fallopian tube or primary peritoneal cancer
Recurrent = In combo with carboplatin and gemcitabine for treatment of adults with first recurrence of platinum-sensitive epithelial ovarian, fallopian tube or primary peritoneal cancer, who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGFR-targeted agents
Or
In combination with paclitaxel, topotecan, or pegylated liposomal doxorubicin for treatment of adult with platinum-resistant recurrent epithelial ovarian, fallopian
tube or primary peritoneal cancer, who received no ≤2 prior chemotherapy regimens and who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGFR-targeted agents
What is the CDF criteria for Avastin?
1L treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer
• Chemotherapy-naïve
One of the following:
• FIGO stage III debulked but residual disease >1 cm
• Stage IV disease
• Stage III at presentation and requiring neo-adjuvant chemotherapy due to low likelihood of optimal primary surgical cytoreduction
• Bevacizumab dose to be 7.5mg/kg every 3 weeks
Maximum of 18 cycles
How does Avastin work?
It is an anti-angiogenic.
Bevacizumab is a humanised monoclonal antibody directed against VEGF-A
• Bevacizumab prevents interaction of VEGF-A with
VEGFR-1 and -2
How does Bev potentiate PARP inhibitors?
Anti-angiogenic agents can induce hypoxia, leading to homologous recombination gene downregulation
and subsequent HRD. Induction of HRD in cells that would otherwise be HRD-negative could increase vulnerability to PARP inhibitors
Which trials led to the licensing of bevacizumab for first-line treatment in OC?
Licensing for first-line bevacizumab is based on data
from the key registrational trials ICON7 and GOG 0218
In ICON7, which subgroup of patients achieved a significant OS benefit from bevacizumab treatment?
High risk patients
Which trials led to Bevacizumab gaining approval in the PSR setting?
OCEANS and GOG-0213 studies
What was OCEANS?
Phase III placebo-controlled maintenance study of gemcitabine, carboplatin and bevacizumab
• Platinum sensitive relapsed ovarian cancer with measurable disease
Primary endpoint was investigator assessed PFS
What was GOG-0213
Phase III randomised study of bevacizumab and secondary cytoreductive surgery in PSR OC
• Platinum-sensitive recurrent epithelial
ovarian cancer
• CR to ≥3 cycles of front-line platinum/taxane therapy
Primary endpoint was OS
What was the outcome of OCEANS?
In the OCEANS study, the addition of bevacizumab to chemotherapy resulted in a significant 4 month improvement to median PFS (12.4 months for the
bevacizumab arm vs. 8.4 months for
placebo)
• The risk of disease progression or death was significantly reduced by 52% for patients receiving additional bevacizumab compared to placebo (HR
0.484; [95% CI 0.388–0.605] p<0.0001)
• There was no significant difference in median OS was consistent between treatment arms; 33.6 for the
bevacizumab arm vs. 32.9 months for placebo (HR 0.95; log rank p=0.65)
What was the outcome of GOG-0213
In the GOG-0213 study, patients that received combination followed by maintenance bevacizumab had a non-significant 4.9 month improvement in OS (HR 0.829 [95%CI 0.683–1.005]) p=0.056)
• PFS, a secondary endpoint, did show a significant improvement with bevacizumab treatment vs. placebo (HR 0.63 [95% CI 0.53, 0.74]; p<0.0001*)
• A sub-group analyses also showed that prior treatment with bevacizumab did not negatively impact OS
What are the most common and adverse effects of bevacizumab?
Proteinuria, hypertension, wound healing complications
What are the most severe adverse effects of bevacizumab?
GI perforations, Haemorrhage, including pulmonary haemorrhage/ haemoptysis, and venous thromboembolism
How is bevacizumab administered?
Once every 3 weeks via IV infusion
