Anti-Angiogenesis Therapy in Gynecologic Malignancies

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Discussion

The reason bevacizumab resulted in an OS advantage in cervical cancer and not in ovarian cancer may lie in the biological differences between these two gynecologic cancers. Ovarian carcinogenesis is characterized by tumor heterogeneity stemming from genomic instability, nonequivalent gene expression, and copy number alterations.......
Another salient difference between epithelial ovarian cancer and cervical cancer with regard to clinical trial endpoints is the role of post-progression therapy. At the 2014 SGO Annual Meeting, Aghajanian and colleagues presented the final analysis of OS in the OCEANS trial that compared the addition of bevacizumab to the carboplatin/gemcitabine doublet vs carboplatin/gemcitabine plus placebo.[67] More than 88% of patients in the bevacizumab-containing arm and 90% of those in the placebo arm went on to receive anticancer therapy, with a median of 5 additional regimens. The chemosensitivity of ovarian cancer makes OS in late-phase clinical trials a controversial and potentially biased metric for multiple reasons. Both imbalanced treatment crossover after randomization and post-progressive therapies can dilute the effect of the study drug on OS. Detecting an OS advantage that derives from an improvement in PFS requires a short median post-progression interval (approximately 6 months),[68] a clinical scenario more often seen in advanced cervical carcinoma.

Conclusion

Anti-angiogenic therapies have a clear role in the treatment of gynecologic cancers. In 2014, the FDA approved the use of bevacizumab in advanced cervical cancer and platinum-resistant ovarian cancer, providing viable options for high-risk subgroups that previously had none. For most patients with gynecologic cancers, the response seen with anti-angiogenic therapy is unlikely to result in cure, and exploration of alternate therapies remains necessary. The discovery of new therapeutic agents and inevitably longer disease-free intervals will give rise to a new population of gynecologic cancer survivors, who will present novel challenges. Multimodal treatment strategies that include surgery, CT, radiotherapy, anti-angiogenesis therapy, and immunotherapy will allow patients with gynecologic malignancies to maximize their survival potential.

Financial Disclosure: Dr. Tewari has served in a limited capacity as a consultant and advisory board member for Roche-Genentech. Drs. Cripe and Liu have no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article