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Abstract
The majority of women with ovarian cancer will experience a recurrence of their disease despite aggressive primary cytoreduction and adjuvant cytotoxic chemotherapy. Notwithstanding the high rate of recurrence, targeted and biologic agents have helped to decrease the dependence on cytotoxic chemotherapy. Bevacizumab, a vascular endothelial growth factor inhibitor, has been shown to cause regression in tumor vasculature, inhibition of angiogenesis and prevention of progenitor cell recruitment. Phase III clinical trials of bevacizumab in patients with primary epithelial ovarian cancer and in patients with platinum-sensitive ovarian cancer have shown an improvement in progression free survival without an appreciable difference in overall survival. The addition of bevacizumab to standard cytotoxic chemotherapy regimens has demonstrated improved response rates, and improved progression free survival. These results have stimulated research in additional angiogenesis inhibitors and trials to further incorporate bevacizumab into the treatment schema for patients with recurrent ovarian cancer.
Keywords::
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
Key issues
Bevacizumab (Avastin®; Genetech, Inc., CA, USA) is a recombinant monoclonal IgG antibody that binds to and inhibits activity of VEGF-A.
Net effect is regression of tumor vasculature, inhibition of angiogenesis and prevention of progenitor cell recruitment.
Key Phase III trials supporting the use of bevacizumab in the treatment of primary epithelial ovarian cancer are GOG 218 and ICON7; use in platinum-sensitive recurrent ovarian cancer has been evaluated in the OCEANS trial.
GOG 218 showed a statistically significant increase in progression-free survival (PFS) of 14 versus 11 months, and a hazard ratio of 0.72; 95% CI: 0.63–0.82. No improvement in overall survival (OS) was seen.
ICON7 demonstrated increase in overall response rate of 67 versus 48% when given bevacizumab (hazard ratio of 0.81; 95% CI: 0.70–0.94; p < 0.0041). The median PFS with bevacizumab was 24 versus 22 months. No appreciable difference in OS was shown.
OCEANS trial demonstrated a median PFS in the control arm of 8.4 versus 12.4 months in the bevacizumab arm. Again, no difference was seen in OS (33 vs 35 months in the placebo arm).
The Gynecologic Cancer Intergroup consensus concluded that even modest improvements in PFS should not be dismissed in the treatment of platinum-sensitive recurrent ovarian cancer, as this may be reflective of disease control and tumor shrinkage. Clinically, this notion needs to be weighed against a woman’s performance status and quality of life.
End-of-life-care discussions should be conducted with all patients with a clear understanding that treatment has shown no improvement in OS.
Main toxicities include hypertension and proteinuria. Gastrointestinal perforations can occur in approximately 3% of bevacizumab-treated patients with a 30-day mortality approaching 25–50%.
Cost of treatment with bevacizumab can be exorbitant. Cost analyses using ICON7 data show that using bevacizumab at 7.5mg/kg and for shorter maintenance periods can be cost–effective.
GOG 213 is currently accruing patients and evaluating the role of secondary cytoreduction and/or the addition of bevacizumab with regard to the duration of OS, PFS and quality of life.
Additional biologic agents currently being studied in Phase II trials are AMG 386 and PARP inhibitors. Continued research and development of biologic and targeted agents will help decrease the dependence on cytotoxic agents in hopes of improving PFS, OS and quality of life.