Case 2: Maintenance in BRCA1/2wt, HR-Proficient Ovarian Cancer

Thomas C. Krivak, MD: Here are the NCCN [National Comprehensive Cancer Network] guidelines looking at when bevacizumab is used up front. The BRCA1/2 wild type were unknown. This is the little box up top here, this is bevacizumab plus olaparib. There are bright people sitting on these panels deciding some of these guidelines, but they were thinking that PAOLA was probably going to get an all-comers and ITT [intent-to-treat], and I was surprised. I was happy because we need to move to biomarkers, but I was surprised that they cut out the HRD [homologous recombination deficiency]. It will be interesting; just like you said, Shannon, are they going to go ahead and change the recommendation?

Shannon Westin, MD: Revise that, yes.

Thomas C. Krivak, MD: What this does is exactly what you guys have said. We have lots of options and depending upon [adverse] effects, depending upon how patients are doing, it will give us options. We had a patient who was on bevacizumab/olaparib based off ESMO [the European Society for Medical Oncology Congress], and she’s had 2 blood transfusions and was dose reduced, which I was surprised about. She’s BRCA2 mutated in her tumor, so we’re going to switch her over to another PARP inhibitor and take her off bevacizumab but keep her on PARP. Giving us these options is what’s key. [Adverse] effects drove her off the combination, so being a BRCA mutation type of patient, I don’t think any of us are willing to not treat her or at least try to treat her with PARP for a little longer. Any thoughts on these, guys?

Shannon Westin, MD: No, you covered it. It will be interesting to see if anything changes now that we have all the indications. Then, we don’t really get to talk about it, but it’s important to mention the VELIA data and that we mention the trial design and the chemotherapy with veliparib. If that does get an approval, then we’ll have to come back to this situation and see where that fits in for all these patients. For now, without an indication, we’re making the decision between these 3 agents.

Thomas C. Krivak, MD: Yes, excellent. If this patient was BRCA1/2 wild type and HR [homologous recombination]-proficient, what would you recommend for maintenance therapy after carboplatinum/Taxol[paclitaxel]/bevacizumab for primary therapy? The options are bevacizumab, bevacizumab plus olaparib, niraparib, observation, or clinical trial. Any time we talk about clinical trial, that should be where we go.

Shannon Westin, MD: Yes.

Thomas C. Krivak, MD: We have great strides in patients with BRCA mutations and great strides in HRD, we have first open, hopeful we’ll get to reopen. We try to put patients on the ATHENA study. The bottom line is that we’ve made great progress, and if we can get patients on a clinical trial, that’s what we need to do. Most of our patients, unfortunately, don’t go on to clinical trial. For HR-proficient, if this patient had a lot of ascites, I would use bevacizumab. If the patient didn’t have a lot of ascites, I would probably switch over to single-agent niraparib and do some type of switch maintenance. I would not use bevacizumab/olaparib.

Shannon Westin, MD: Yes. For her, where we started bevacizumab, I would continue bevacizumab, and then if I hadn’t, I would talk to her, as I mentioned before, and review all those data around the niraparib single agent and try to make the best decision possible. I agree, the clinical trials, especially for this proficient group, is where we’re hoping we’re going to see more of an impact when those are all reported out.

Chad Hamilton, MD: Yes, I would agree. I would leave this patient on bevacizumab as maintenance. I don’t think this is a scenario where you’re getting enough mileage out of your PARP to add it. I worry about some of the cost effectiveness analyses that have been done looking at this preliminarily. I would stick with single-agent bevacizumab maintenance in this scenario.

Shannon Westin, MD: Yes.

Thomas C. Krivak, MD: We all agree: the FDA got it right and did not give the bevacizumab/olaparib in ITT all-comers. Nobody wanted to add olaparib, very nice.

Transcript edited for clarity.