Medicine Matters oncology

We're just wrapping up ESMO 2019. And interestingly, we left the best for last. We just heard some very intriguing data on the use of PARP inhibitors in metastatic castration-resistant prostate cancer that has really failed androgen signaling inhibition, for the most part chemotherapy as well.

These were men who harbored mutations in DDR genes, DNA damage response and repair genes. And specifically, I would say that the main driver of the results that we saw was mutations in BRCA2 that we all know is a low-hanging fruit when you're looking at the biology of this disease.

So this trial was interesting in the following way. They actually recruit patients who had received prior either abiraterone or enzalutamide and had, for the most part, maybe received chemotherapy, meaning it was allowed. Then they randomized them 2:1 to either receive olaparib or receive a physician's choice drug that had to be the alternate. Let's say they were on abi. They would go on enzalutamide. If they had been on enzalutamide, they would go on abiraterone.

So unfortunately, this is standard practice. So they compared olaparib and how it performed versus standard practice. And they only did it for patients who harbored such mutations. And they used an assay that's commercially available, which makes it actually easy to translate into clinical practice, the foundation assay.

So the data was positive. It was roughly 400 patients, but 125 of them had the BRCA2 mutation in their tumor. And I personally believe because I was discussing the trial that these results carried the weight of the whole study. And I'm not speaking as a statistician but as a clinician.

Even if you look at how these men performed who had the BRCA2, they stand at a much higher level of performance than the rest. But even if you look across the whole cohort or the cohort that was BRCA and ATM, you see these very positive results. So the primary endpoint for statistical purposes was met.

Now it lies with the regulatory agencies, with the clinicians to figure out what is the actual target group that we're going to use this drug in. But there is a message that's much stronger than just introducing olaparib in prostate cancer like we have in breast and ovarian cancer. It's the message that for the first time, we have a targeted therapy in prostate cancer that has delivered positive results. And it's actually opening up this era of moving away from a one-fits-all approach to just treating in a more wise fashion and based on the molecular classification. And that's my main take-home message from this study.