Other Factors Considered When Adding PARP Inhibitors to Metastatic Prostate Cancer Therapy

EP: 1.Diagnosing Metastatic Prostate Cancer

EP: 2.Biomarker Testing in Metastatic Prostate Cancer

EP: 3.Treatment Options for Metastatic Prostate Cancer

EP: 4.The Role of PARP Inhibitors in Prostate Cancer

EP: 5.Rucaparib for Prostate Cancer

EP: 6.Advances in Metastatic Castration-Resistant Prostate Cancer

EP: 7.Routinely Ordered Testing for Metastatic Prostate Cancer

EP: 8.Biomarker Testing Protocols for Metastatic Prostate Cancer and What to Look For

EP: 9.BRCA1/2 in Metastatic Prostate Cancer

EP: 10.Systemic Treatment Options for Metastatic Castration-Resistant Prostate Cancer

EP: 11.Selecting Appropriate Treatment and Monitoring Patients on Metastatic Prostate Cancer Therapy

EP: 12.The Role of PARP Inhibitors and Adverse Events in Metastatic Prostate Cancer Therapy

Now Viewing

EP: 13.Other Factors Considered When Adding PARP Inhibitors to Metastatic Prostate Cancer Therapy

EP: 14.Patient Access and Metastatic Prostate Cancer Therapy

EP: 15.Sequencing Strategies for Metastatic Castration-Resistant Prostate Cancer Therapy

EP: 16.Exciting Advances in the Therapeutic Space and Clinical Pearls for Treating Metastatic Prostate Cancer

EP: 17.Recap: Recommendations for PARP Inhibitor Use in Prostate Cancer

EP: 18.Recap: Testing and Treating Metastatic Castration-Resistant Prostate Cancer

Matthew Fowler: In addition to the required testing and mutational profiles, are there other characteristics or factors that you consider when deciding whether to add a PARP inhibitor to a patient’s treatment plan?

Alicia Morgans, MD, MPH: I always think about prior therapies. I want to make sure my patient fits the profile of the label that came down with the approval. That’s important. I also think about which mutation an individual patient has in his germline, because there’s some difference, first of all, in the approval. For example, if a patient has a PALB2 mutation, that isn’t an approved mutation to target with rucaparib. Not that it wouldn’t necessarily work—we don’t have enough data—the label just doesn’t cover that mutation. We want to make sure that we have the proper mutations for the drug. I also think about the mutation because PARP inhibitors seem to have differential effectiveness against different mutations.

I want to couch that comment by saying that when the PROfound trial assessed response to treatment with olaparib by mutation, it was completely exploratory. That wasn’t powered to definitively show that any mutation had a phenomenal response or didn’t have a good response. Additional data come from the TOPARP-B trial, which also included exploratory analyses by mutation type in relation to the effect of olaparib.

But we did see in these trials that there was perhaps less of a reduction in tumor size for patients who had a mutation in ATM. This was true in both the PROfound study, where we looked at olaparib, and the TRITON2 study, where rucaparib was assessed. If a patient has an ATM mutation and has clinical progression with a lot of symptoms and maybe visceral involvement of the liver or some other crisis situation, like cord compression, I might not reach for a PARP inhibitor for that ATM mutation. Because I really need a fast response and I need it to be very effective and strong, I might reach for chemotherapy. That’s an extreme example, but it’s something we think about.

If the patient has a BRCA2 mutation, besides being the most common mutation, it also seems to be a pretty responsive mutation. If I have a patient who has disease progression and maybe some clinical symptoms, but has a BRCA2 mutation, then I might feel more confident that olaparib or even rucaparib will be able to get that cancer under control maybe more quickly than if that patient had an ATM or CDK12 mutation. The mutation itself and the way the cancer is progressing both play a role in that decision-making process.

This transcript has been edited for clarity.