A medical oncologist discusses situations in which he might recommend abiraterone alongside a PARP inhibitor as first-line treatment for patients with mCRPC.
Case: A 65-Year-Old Man With Prostate Cancer
Daniel J. George, MD: When I think about the practice today for patients with metastatic castrate-resistant prostate cancer, despite the overwhelming level 1 evidence for using novel hormonal agents early, there are still going to be circumstances where we have patients for whom we don’t use a novel hormonal agent early in the disease course. A couple of these would be patients who are presenting with locally advanced disease and we’re starting on androgen deprivation therapy and radiation therapy, our standard of care, 2 years of androgen deprivation therapy. Some patients within that 2-year period are going to progress, and those patients who develop early progression with hormones and radiation, they’re castrate-resistant. If those patients have metastatic disease, and with much of our novel imaging, we’re going to find these are the reasons these patients are progressing, not within their radiated prostate bed, but outside of that radiation bed. That progression will be seen either on traditional or novel imaging. These are the patients today who I think are best representative of the PROpel data. If they’re BRCA-mutated, these are the patients for whom I’m going to want to consider using androgen deprivation therapy, a novel hormonal agent like abiraterone, and a PARP inhibitor like olaparib. It’s precisely because of the PROpel data and how powerful they are that I want to use that in somebody like that, who has this accelerated course progression to castration resistance within the first 2 years of hormones and radiation.
Another scenario is like the case we presented here, where somebody had a BRCA mutation up front, rapid progression following surgery, relatively rapid progression following androgen deprivation therapy and abiraterone, and then further progression after response to docetaxel chemotherapy. Because the patient had a prior response to abiraterone, due to a break from abiraterone with docetaxel, I’d consider rechallenging that patient with abiraterone and adding olaparib. Because now they’re somebody who falls into the PROfound study situation, where our expectations for median progression-free survival are modest, maybe 7 months or so. That’s the population of patients where I’d like to extend it as much as possible. This olaparib use is going to be the best last treatment we can offer that patient with a BRCA mutation, so we’re going to want to maximize it however we can. If they tolerated the abiraterone well, I’m going to want to rechallenge that with my olaparib to see if I can get anywhere close to the results we saw with PROpel rather than the results we saw with PROfound.
Those are some of the scenarios where I think even today, despite the use of our novel hormonal agents increasing in the hormone-sensitive disease space, there’s still room for these PROpel data to use them and extrapolate them into our practice.
Transcript edited for clarity.