Expanding Role of PARP Inhibitors in Advanced Ovarian Cancer - Episode 17
Ursula A. Matulonis, MD: Regarding drugs that inhibit angiogenesis—drugs like bevacizumab that have now been FDA approved in a number of settings, drugs like cediranib that are in clinical trials—we really do have to follow the FDA guidelines around the use of these agents. So, for bevacizumab, it’s been approved for patients with stage III or stage IV advanced ovarian cancer who have residual disease at the completion of surgery, using that drug with chemotherapy and then as maintenance therapy for up to 22 cycles post-initial chemotherapy. In the recurrent setting, bevacizumab has two approvals, one use with chemotherapy in women who have platinum-sensitive recurrent disease based upon the OCEANS trial and GOG-213. So bevacizumab can be added to either carboplatin/gemcitabine or carboplatin/paclitaxel.
And, if patients have platinum resistant cancer, meaning that the cancer has started to grow within six months of completion of carboplatin, then the trial called the AURELIA trial led to the approval of bevacizumab in platinum-resistant patients. So either combining bevacizumab with weekly paclitaxel, pegylated liposomal doxorubicin, or topotecan shows a progression-free survival of about 3 to 4 months. And that progression-free survival is really notably extended in patients receiving weekly paclitaxel. For pegylated liposomal doxorubicin or topotecan, the results are a little bit less impressive.
Michael Birrer, MD: The role of pazopanib in ovarian cancer I think is problematic. If I were being frank, I don’t think it has a role. It’s a randomized phase III trial which demonstrated prolongation of progression-free survival utilizing pazopanib. But it needs to be pointed out that it never went to approval. The company abandoned the drug. And my own experience with it in other tumors has been that it has a toxicity profile that is essentially unacceptable. Pazopanib is a tyrosine kinase inhibitor in the same family as cediranib, sunitinib, so on and so forth.
Pazopanib has a significant, significant amount of fatigue associated with it. And when used in maintenance therapy it causes so much fatigue in patients that I think the companies and the regulators realized that this was not an effective maintenance therapy. In addition, what complicates it or makes it even clearer is that you have a drug like bevacizumab where none of those issues are a problem. Now one could complain that bevacizumab has hypertension as an adverse event, but so does pazopanib because it’s an anti-angiogenic agent.
Transcript Edited for Clarity