The lingering doubt remains whether the nonmetastatic patient should get abiraterone, and the issue is in the STAMPEDE trial that included these patients. There were not a lot of mortality events in the nonmetastatic population. The survival difference here was driven by the metastatic patients. The investigators did look at the interaction of metastasis versus no metastasis and they showed there was no interaction. Their position is that both metastatic and nonmetastatic patients should receive abiraterone; however, the fact is that the number of events in the nonmetastatic population was low for mortality events.
You probably have 2 camps right now. One camp suggests that everyone, metastatic or nonmetastatic, should get abiraterone; the other camp says that only patients with metastatic disease should get abiraterone acetate.
On the other hand, you also have the extreme of the LATITUDE trial, which was in high-risk metastatic patients. There is not a right or wrong answer. I tend to fall right in the middle, which is the metastatic patients. That’s right in the middle between nonmetastatic patients and high-risk metastatic patients.
Will we start seeing bigger breakthroughs with either PARP inhibitors or immunotherapy for prostate cancer in the next year?
That could be. The trials are ongoing. A phase III trial is now ongoing, looking at olaparib (Lynparza) as second-line treatment in select patients post one of the androgen inhibitors. We'll have to wait and see. I’m not sure we'll have an answer next year.
[Regarding immunotherapy], checkpoint inhibitors are being looked at and it seems like patients that are exposed to enzalutamide might have an upregulation of PD-L1 in the tumors. There was some activity shown in this population in a small cohort. There is hope that there will be benefit with the checkpoint inhibitors in selected patients. We'll have to wait and see for both the PARP inhibitors and the checkpoint inhibitors. There is pembrolizumab (Keytruda) and atezolizumab (Tecentriq) being looked at in this population, as well.
If these checkpoint inhibitors one day get FDA approval, how could we try to fit them into the paradigm in terms of sequencing?
The sequencing question is getting more and more complicated, so all of these drugs are now moving up to the castration-sensitive phase, as we saw in docetaxel now in the castration-sensitive phase. There are trials looking at the combination of enzalutamide (Xtandi) and abiraterone acetate with ADT in castration-sensitive disease and multiple combinations are being looked at.
Right now, both [the PARP inhibitor] olaparib, for example, and PD-1/PD-L1 inhibitors, like pembrolizumab or atezolizumab, are being looked at in the castration-resistant phase. That actually is a space that might warrant looking at this because it looks like the older agents, like docetaxel, abiraterone, and enzalutamide, are all moving to the castration-sensitive space. It might make sense anyway to look at these more novel agents, such as olaparib or pembrolizumab, for castration-resistant disease. The field is evolving very quickly.
What ongoing research are you a part of that you would like to share?
In the space of prostate cancer, we have a phase I, investigator-initiated trial that is looking at a combination of abiraterone, enzalutamide, and cabazitaxel. This is a triplet combination. We're looking at it in the castration-resistant space of the disease. Cabazitaxel is also a taxane like docetaxel, but it’s not as neurotoxic. It has more myelosuppression but, given the lack of neurotoxicity, you can give it for a prolonged period of time. We'll wait and see what the trial shows.