PARP Inhibitor Olaparib Delivers Strong Results in Selected Prostate Cancer Cases

This transcript has been edited for clarity. 

Hello. I’m Dr Maurie Markman, from City of Hope. I’d like to briefly discuss a small study, not a large, randomized, controlled clinical trial. One may ask, how do you draw major conclusions on a small trial, which I’ll identify in a moment. 

I want to make a point that sometimes small trials can have a major impact, particularly when the results are impressively favorable for a subset of the population, that we might want to consider using sooner rather than later in terms of our ultimate paradigms. The study I’m referring to was titled, “Olaparib Without Androgen Deprivation for High-Risk Biochemically Recurrent Prostate Cancer Following Prostatectomy: A Nonrandomized Controlled Study.” 

There are many debates about the optimal therapy in prostate cancer with rising prostate-specific antigen (PSA) in people who might not be symptomatic but just have a biomarker. What is the impact on quality of life? What is the cost of the therapy? What is the ultimate impact on survival? 

This was a nonrandomized, controlled trial, looking at individuals who had biochemically recurrent prostate cancer after radical prostatectomy. These were genetically unselected patients at four sites, treated from May 2017 to November 2022. Again, this analysis included people who might not have had a BRCA mutation. 

Eligible patients had biochemically recurrent disease following radical prostatectomy, a PSA doubling time of 6 months or shorter, an absolute PSA value of 1.0 ng/mL or higher, and a testosterone level of 150 ng/dL or higher.

There were 51 individuals, obviously all male, who participated in this effort, and 13 individuals had what they described as a PSA50 response — so at least a 50% reduction lasting at least a month with the use of olaparib. That was a 26% response rate. 

The point to be made here is that we saw responses in individuals who had documented homologous recombination deficiency, as one would believe would be the case for a PARP inhibitor. But also, very importantly, 11 patients in this analysis had documented BRCA2 alterations, and 100% — all 11 patients — experienced an objective response. 

As one might speculate based on what we know about PARP inhibitors, certainly in ovarian cancer and breast cancer, we see that not only do the data support the restriction of the use of this class of drugs — this drug in particular — in individuals who have documented homologous recombination efficiency, but also there was a very high response rate in individuals with a BRCA mutation. 

Yes, we need to see more data confirming this observation, and I would argue we don’t need randomized phase 3 trials at this point. We need more data demonstrating this [response], and assuming that occurs, then this is potentially a very rational strategy and a reasonably well-tolerated therapy to employ in a subset of patients following recurrence after radical prostatectomy in this clinical setting. 

Again, there is more to discuss and more to say, but I think this is a very important analysis and a very striking result as to where PARP inhibitors might be relevant in the setting of recurrent prostate cancer.

Thank you for your attention.