A Phase III Clinical Trial of Bevacizumab With IV Versus IP Chemotherapy in Ovarian, Fallopian Tube and Primary Peritoneal Carcinoma

Trial ID # NCT00951496; GOG-252
Phase III
Drug Class Angiogenesis Inhibitors: VEGF
Drug Name Bevacizumab
Alternate Drug Names immunoglobulin G1 (human-mouse monoclonal rhuMab-VEGF gamma-chain, anti-VEGF monoclonal antibody, Avastin
Drugs in Trial Bevacizumab, Carboplatin, Cisplatin, Paclitaxel
Eligible Participant

Newly diagnosed stage II-IV epithelial ovarian cancer

Patients Enrolled

1560

Therapy Setting

First-line

Study Design

Open-Label, Randomized

Endpoints

PFS, OS, evaluated per RECIST

Efficacy

Regimens:
IV CarboPt+Pac: IV paclitaxel 80 mg/m2 once per week with intravenous (IV) carboplatin area under the curve 6
IP CarboPt+Pac: IV paclitaxel 80 mg/m2 once per week with IP carboplatin area under the curve 6
IP CisPt+Pac: once every 3 weeks IV paclitaxel 135 mg/m2 over 3 hours day 1, IP cisplatin 75 mg/m2 day 2, and IP paclitaxel 60 mg/m2 day 8
--all regimens also received bevacizumab 15mg/kg IV every 3 weeks in cycles 2 to 22.

IV CarboPt+Pac+Bev w/ Bev maint vs IP CarboPt+Pac+Bev w/ Bev maint vs IP CisPt+Pac+Bev w/ Bev maint:
PFS: 24.9 vs 27.4 vs 26.2 months, HR: 0.925 (0.802-1.07, n.s.), 0.977 (0.847-1.13, n.s.)
OS: 75.5 vs 78.9 vs 72.9 months, HR: 0.949 (0.799-1.128, n.s.), 1.05 (0.884-1.24, n.s.)

Exploratory analysis stage II/III disease and optimally resected (residual disease of 1 cm or less) (n=1,380):
PFS: 26.9 vs 28.7 vs 27.8 months, HR: 0.921 (0.789-1.07, n.s.) and HR: 0.966 (0.828-1.13, n.s.)
OS: 80.0 vs 84.7 vs 76.3 months (n.s.)

Clinically Significant Adverse Events

IV CarboPt+Pac+Bev w/ Bev maint vs IP CarboPt+Pac+Bev w/ Bev maint vs IP CisPt+Pac+Bev w/ Bev maint:
Serious AE: 25 deaths, due to toxicity (8 vs 7 vs 10)
Grade 3-4 AE: hypertension (11.9 vs 14.3 vs 20.5%), infections (11.5 vs 17.2 vs 17.7%), nausea and vomiting (5.1 vs 4.7 vs 11.0%)

Conclusion

Compared to the IV reference arm, PFS was not significantly increased with either IP regimen

Reference

Walker JL et al. Randomized Trial of Intravenous Versus Intraperitoneal Chemotherapy Plus Bevacizumab in Advanced Ovarian Carcinoma: An NRG Oncology/Gynecologic Oncology Group Study. J Clin Oncol (2019) 37(16):1380-1390
https://www.ncbi.nlm.nih.gov/pubmed/31002578