Chad Hamilton, MD: Shannon, tell us what to do on this PARP-after-PARP inhibitor issue.
Shannon Westin, MD: Let me comment first that the addition of bevacizumab is exactly what I would have done. I consider it with paclitaxel, but also use pegylated liposomal doxorubicin based on the recent paper that came out that showed that had a benefit over gemcitabine, carboplatin, and bevacizumab. As far as re-resection is concerned, this patient had a multifocal recurrence, which even prior to [Robert] Coleman, [MD’s,] GOG-0213 data, that pushed me away from the consideration of re-resection. With that being said, we’re eagerly anticipating the results of DESKTOP III, which are going to be presented at ASCO [the American Society of Clinical Oncology annual meeting] this year, virtually. If there is a way to do better selection, rather than saying that somebody is a surgical candidate versus somebody using strict criteria to determine who might benefit from secondary cytoreduction, I would definitely consider that. But for her, it sounds like it was more of a multifocal.
To your point, we don’t know the answer for PARP-after-PARP. There are a number of interesting studies that are ongoing looking at if you can do PARP alone. The OReO study is completely enrolled now. That study was in secondary maintenance, so they got secondary maintenance with olaparib, ultimately progressed, got retreated with a paclitaxel or a carboplatin-based chemotherapy, had another response to therapy, and then are randomized again to olaparib. That will be very informative. It’s not exactly informative to our patients who are going to be getting these PARP inhibitors up front, but it will be interesting to see if there’s activity in that setting.
I am interested in the combinations here. We have a number of trials that are combining different antiangiogenics, immune oncology agents, and tyrosine kinase inhibitors across a number of survival pathways. That is going to be incredibly informative to see if you can overcome that so-called PARP resistance and go back to that well. There’s a lot to be learned here now.
Chad Hamilton, MD: Alright, great discussion. This is another one of those that we could go for hours on, in and of itself. What does the NCCN [National Comprehensive Cancer Network] tell us? We’ve certainly hit on this. We can consider secondary cytoreductive surgery; GOG-0213 as Tom mentioned, did not show a benefit. Dr Coleman has got some additional information that’s going to be coming out soon on that topic, but we also await the German group’s input as well, and that’s going to be interesting to see. If we have conflicting data, we can rationalize anything that we do at that point. I agree with you on the multifocal recurrence aspect of this as well; I’d probably not re-resect in multifocal recurrence.
As far as chemotherapy goes in this case, certainly combination platinum-based chemotherapy is the preferred regimen, and then consideration of maintenance. If the patient has been on carboplatin/Taxol [paclitaxel]/bevacizumab, previously, then bevacizumab is favored again. In other patients who have not been on bevacizumab, then consider 1 of the 3 PARPs that are great options for us at this point.
Transcript edited for clarity.