Bevacizumab Plus Chemotherapy in Advanced Ovarian Cancer


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ON JUNE 13, 2018, bevacizumab (Avastin) was granted approval for treatment of epithelial ovarian, fallopian tube, or primary peritoneal cancer in combination with carboplatin and paclitaxel, followed by single-agent bevacizumab, for stage III or IV disease after initial surgical resection1,2. The U.S. Food and Drug Administration granted bevacizumab Orphan Drug designation for this indication. 

OF NOTE

Bevacizumab has boxed warnings for gastrointestinal perforation, surgical and wound-healing complications, and hemorrhage.

Supporting Efficacy Data 

APPROVAL WAS BASED on findings in the phase III double-blind GOG-0218 trial, in which 1,873 women were randomized to receive carboplatin plus paclitaxel without bevacizumab (CPP group, n = 625), carboplatin plus paclitaxel with bevacizumab for up to 6 cycles (CPB15 group, n = 625), or carboplatin plus paclitaxel with bevacizumab for 6 cycles followed by single-agent bevacizumab for up to 16 additional doses (CPB15+ group, n = 623). Bevacizumab was given at 15 mg/kg every 3 weeks. 

The estimated median progression-free survival was 18.2 months in patients receiving bevacizumab with chemotherapy followed by single-agent bevacizumab (hazard ratio [HR] = 0.62, P < .0001, vs chemotherapy alone), 12.8 months for those receiving bevacizumab with chemotherapy without single-agent bevacizumab (HR = 0.83, P = not significant, vs chemotherapy alone), and 12.0 months in those receiving chemotherapy alone. The estimated median overall survival was 43.8 months with bevacizumab plus chemotherapy followed by bevacizumab vs 40.6 months with chemotherapy alone (HR = 0.89). 

How It Works 

BEVACIZUMAB BINDS vascular endothelial growth factor (VEGF), preventing the interaction of VEGF with its receptors (Flt-1 and KDR) on the surface of endothelial cells. The interaction of VEGF with its receptors leads to endothelial cell proliferation and new blood vessel formation in in vitro models of angiogenesis. Administration of bevacizumab in xenotransplant models of colon cancer in nude athymic mice resulted in reduction of microvascular growth and inhibition of metastatic disease progression. 

How It Is Used 

THE RECOMMENDED bevacizumab dose for stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer following initial surgical resection is 15 mg/kg every 3 weeks with carboplatin and paclitaxel for up to 6 cycles, followed by 15 mg/kg every 3 weeks as a single agent until the earlier of a total of up to 22 cycles or disease progression. Bevacizumab should be withheld at least 28 days prior to elective surgery. In patients undergoing surgery, bevacizumab should not be given until at least 28 days after surgery and full healing of the wound. 

No dose reductions of bevacizumab are recommended. Bevacizumab treatment should be discontinued for the following adverse reactions: gastrointestinal reactions, tracheoesophageal fistula, grade 4 fistula, and fistula formation involving any internal organ; wound-healing complications requiring medical intervention and necrotizing fasciitis; grade 3 or 4 hemorrhage; severe arterial thromboembolism and grade 4 venous thromboembolism; hypertensive crisis and hypertensive encephalopathy; any posterior reversible encephalopathy syndrome; nephrotic syndrome; severe infusion reaction; and any congestive heart failure. 

Safety Profile 

THE MOST COMMON adverse events of any grade (incidence >10%) in patients receiving bevacizumab in clinical trials were epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, and exfoliative dermatitis. 

Bevacizumab has boxed warnings for gastrointestinal perforation, surgical and wound-healing complications, and hemorrhage. Bevacizumab also carries warnings/precautions for perforation or fistula, arterial thromboembolic events, venous thromboembolic events, hypertension, posterior reversible encephalopathy syndrome, renal injury and proteinuria, infusion reactions, embryofetal toxicity, ovarian failure, and congestive heart failure. Blood pressure and urine protein should be monitored. Patients should be advised not to breastfeed while receiving bevacizumab. ■

REFERENCES 

1. U.S. Food and Drug Administration: FDA approves bevacizumab in combination with chemotherapy for ovarian cancer. Available at www.fda.gov/ Drugs/InformationOnDrugs/ApprovedDrugs/ucm610664.htm. Accessed July 16, 2018. 

2. Avastin (bevacizumab) injection prescribing information, Genentech, Inc, June 2018. Available at www.accessdata.fda.gov/drugsatfda_docs/label/2018/125085s323lbl.pdf. Accessed July 16, 2018.


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