Metastatic CRPC: Advent of PARP Inhibitors

EP: 1.Breakthroughs in Imaging Modalities for Prostate Cancer

EP: 2.Prostate Cancer Imaging: Unmet Needs and Knowledge Gaps

EP: 3.Recent Progress in the Prostate Cancer Treatment Landscape

EP: 4.Key Unmet Needs in Prostate Cancer Management

EP: 5.Goals of Treatment for Non-metastatic Castration-Resistant Prostate Cancer

EP: 6.nmCRPC: Clinical Trial Data on AR Inhibitors

EP: 7.AR Inhibitors in nmCRPC: Real-World Data

EP: 8.Importance of Quality of Life When Choosing Therapy for nmCRPC

EP: 9.Non-metastatic Castration-Resistant Prostate Cancer: Patient Monitoring Strategies

EP: 10.Optimizing Care for Patients With Non-metastatic CRPC

EP: 11.Treatment Goals for Patients With Metastatic Hormone-Sensitive Prostate Cancer

EP: 12.Factors in Selecting Therapy for Patients With Metastatic Hormone-Sensitive Prostate Cancer

EP: 13.mHSPC: Use of Triplet Therapy

EP: 14.Metastatic Hormone-Sensitive Prostate Cancer: Data From ARASENS and ARANOTE

EP: 15.Metastatic Hormone-Sensitive Prostate Cancer: Data From ENZAMET and ARCHES

EP: 16.Metastatic Hormone-Sensitive Prostate Cancer: Data from TITAN and PEACE-1

EP: 17.Educating Patients on Treatment Options in Metastatic HSPC

EP: 18.Novel Treatment Modalities in Metastatic Hormone-Sensitive Prostate Cancer

EP: 19.Overview of the Metastatic Castration-Resistant Prostate Cancer Treatment Paradigm

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EP: 20.Metastatic CRPC: Advent of PARP Inhibitors

EP: 21.Practical Application of PARP Inhibitors in Metastatic CRPC

EP: 22.IO Therapy in mCRPC and Clinical Pearls

Transcript:

Alan Bryce, MD: There’s a new class of drugs in CRPC [castration-resistant prostate cancer]; so far it’s just CRPC. Dr Heath, what about PARP inhibitors? We have a wealth of data on 4 different PARP inhibitors. A lot of clinical trials have come out. How would you summarize this space on these 4 drugs?

Elisabeth Heath, MD, FACP: What makes it hard is how people show up to the party. It used to be, “I’m showing up, I look a certain way and that’s it,” but nowadays it’s, “I’ve had this, I’ve had that, I was over at the other party but now I’m here.” Everybody is coming in looking differently, and everyone wants 1 answer. Right off the bat, the answer is that there isn’t 1 answer. Let’s get that straight for our viewing audience. Second, we have 4 studies to talk about that have completed doublets in a different patient group, but the fact that patients have signed up over time to contribute to this is phenomenal, even in the days of having other trials such as lutetium-based studies. That’s a big kudos to our patient population.

We were excited about this last year when we heard about the PROpel trial, which was olaparib plus abiraterone vs abiraterone. Ask yourself: will this only be effective in an HRR [homologous recombination repair] mutation group, or is this for everyone? When that concept got introduced, individuals had already picked sides, so everybody came in saying, “This party is going to look like this.” Having some preconception made discussions interesting because at the same meeting, MAGNITUDE, which was niraparib plus abiraterone vs abiraterone was discussed, and that’s the same thing, is it only in patients with HRR mutation, or is it for everyone?

Part of the difficulty in digesting those 2 pieces of information is, the data wasn’t the same, it’s not the first time this has happened to us in oncology. The PROpel data, which had an update and was well presented by Dr Noel Clarke, part of the discussion was that the data presented were based on PFS [progression-free survival], and we showed some great results there. For audience members who are thinking about this in broad strokes, the answer was in the HRR-mutated group. There was some excitement to say that data look compelling. The newer data and PROpel with final overall survival confirm that feeling. MAGNITUDE was also positive in the HRR group but not as much in the HRR all-comers group; no mutation was required, so that was already uncomfortable. The other 2 studies aren’t exactly in the same space, TALAPRO-2 was nicely presented by Dr [Neeraj] Agarwal, looking at talazoparib plus enzalutamide vs enzalutamide, and the PFS data showed activity in all groups, not just in the HRR mutated.

I’m going to leave those 3 for a second because you expertly presented rucaparib data in the second line for those who’ve had RP [docetaxel]. Then you compared rucaparib vs physician choice, which was RP, or docetaxel. Together, these 4 help us decide if you should combine a RP [docetaxel] plus a PARP inhibitor in everyone, or just in HRR-mutated patients? A bigger picture might be helpful for our audience, as opposed to us getting in the weeds of the numbers. The question is, what do we do with these 3 data sets that are not exactly the same? Perhaps that’s the point—they’re not exactly the same, they’re all standalone trials. If you had a patient with HRR mutation, most likely BRCA2—at least BRCA2, perhaps BRCA1—would you feel comfortable offering olaparib plus abiraterone, olaparib plus niraparib, or enzalutamide plus talazoparib? In general, the answer is yes. But what if it’s all comers and the data still shows positivity? There’s a lot more hand-wringing about was it enough of a difference and what about the adverse effects? I’m going to leave that there because I’m sure our panel will have a lot to say. Your presentation, which was expertly done, looked at rucaparib after RP [docetaxel], do you move on to that? Do you move on to something else? The answer is yes, but how does it stack up to docetaxel? To me, those data that you presented for TRITON3 looked at that question more deeply than the others: should you move on to docetaxel, or is it OK to consider a PARP inhibitor in this setting?

I’m still digesting all the wonderful from ASCO GU [American Society of Clinical Oncology Genitourinary Cancers Symposium], but we should recognize that there are 4 critical combination studies with PARP in the front line and second line, and how are you going to assimilate that depending on how people show up to your party? That’s going to take some time to digest.

Transcript edited for clarity.