ONCAlert | Upfront Therapy for mRCC

Next Steps in Prostate Cancer Research

Targeted Oncology
Published Online:12:00 PM, Thu September 19, 2019

Jorge Garcia, MD: The unmet needs for prostate cancer, overall, reside in identifying a better way for us to screen men who are in need of screening. We want to identify their disease because they may have lethal prostate cancer. I think we still struggle with the prostate cancer screening data, and I think the genomic data are here. That is an area where I feel we’re going to be seeing drastic changes in years to come.

Also needed, the potential combination of systemic therapy with surgery and/or radiation therapy for men with localized disease in an effort to maximize outcome, not only local recurrence but systemic progression, and therefore overall survival. And in the advanced disease setting, the biggest challenge that we’re facing right now is, how do we sequence patients with the many regimens that we have? How do we pick among the agents that we have if we have not been able to compare these trials against each other?

In the M0 [nonmetastatic] space, we have 3 oral agents. Which one is the best? Why pick A, B, or C? In the metastatic castration-naïve setting, regardless of volume, we have 3 large randomized trials, or 4 for that matter, that look at intensification of therapy. Which is the best way to intensify therapy, and what do you do when you get intensified therapy and you progress and become castration-resistant?

None of the trials that we used before for castration-resistant prostate cancer included patients receiving intensification from the get-go. That means that the sequence has been challenged by virtue of how we treat patients earlier; and therefore, the sequence of events and the mechanisms of resistance of those patients may be different than when we developed the older oral agents 5, 7, 10 years ago.

Lastly, the use of genomics. I think that is an area in the field we have actually tried to improve upon. I think the true actionability of genomic testing remains in question for most of our patients with prostate cancer. But clearly, we now have 2 FDA-approved agents. We have PD-1 [programmed cell death protein 1] inhibitors specifically for patients with prostate cancer with microsatellite instability. They require specific genomic data, if you will, to be able to access a PD-1 inhibitor.

In addition to that, we now have very compelling data with DNA repair deficiencies. That means that if you have a patient with a DNA repair deficiency, whether it is a germline deficiency or a somatic deficiency, there are press releases of data looking at PARP [poly ADP ribose polymerase] inhibitors for that patient population with potential impact in response, progression, and possibly even outcome improvement. I think the data with genomics have to be incorporated into what we do on a daily basis, not only from the screening setting but also all the way through the natural history of prostate cancer until the end of castration-resistant disease.

And lastly, how do we incorporate new, emerging imaging technology into our routine clinical practice? PSMA [prostate-specific membrane antigen] PETs [positron emission tomography scans] are obviously very interesting, but they’re expensive and they’re not yet covered in this country. So the reality is, you can actually change management and follow patients when you are using imaging technology that may be able to detect things that we didn’t think patients had before. I think the question remains, again, when you’re looking into the timing of treatment, would identifying disease earlier change my treatment, and therefore change the outcomes of our patients? Or are we simply moving the natural history earlier just by virtue of finding disease with new, novel technology?

Transcript edited for clarity.

Jorge Garcia, MD: The unmet needs for prostate cancer, overall, reside in identifying a better way for us to screen men who are in need of screening. We want to identify their disease because they may have lethal prostate cancer. I think we still struggle with the prostate cancer screening data, and I think the genomic data are here. That is an area where I feel we’re going to be seeing drastic changes in years to come.

Also needed, the potential combination of systemic therapy with surgery and/or radiation therapy for men with localized disease in an effort to maximize outcome, not only local recurrence but systemic progression, and therefore overall survival. And in the advanced disease setting, the biggest challenge that we’re facing right now is, how do we sequence patients with the many regimens that we have? How do we pick among the agents that we have if we have not been able to compare these trials against each other?

In the M0 [nonmetastatic] space, we have 3 oral agents. Which one is the best? Why pick A, B, or C? In the metastatic castration-naïve setting, regardless of volume, we have 3 large randomized trials, or 4 for that matter, that look at intensification of therapy. Which is the best way to intensify therapy, and what do you do when you get intensified therapy and you progress and become castration-resistant?

None of the trials that we used before for castration-resistant prostate cancer included patients receiving intensification from the get-go. That means that the sequence has been challenged by virtue of how we treat patients earlier; and therefore, the sequence of events and the mechanisms of resistance of those patients may be different than when we developed the older oral agents 5, 7, 10 years ago.

Lastly, the use of genomics. I think that is an area in the field we have actually tried to improve upon. I think the true actionability of genomic testing remains in question for most of our patients with prostate cancer. But clearly, we now have 2 FDA-approved agents. We have PD-1 [programmed cell death protein 1] inhibitors specifically for patients with prostate cancer with microsatellite instability. They require specific genomic data, if you will, to be able to access a PD-1 inhibitor.

In addition to that, we now have very compelling data with DNA repair deficiencies. That means that if you have a patient with a DNA repair deficiency, whether it is a germline deficiency or a somatic deficiency, there are press releases of data looking at PARP [poly ADP ribose polymerase] inhibitors for that patient population with potential impact in response, progression, and possibly even outcome improvement. I think the data with genomics have to be incorporated into what we do on a daily basis, not only from the screening setting but also all the way through the natural history of prostate cancer until the end of castration-resistant disease.

And lastly, how do we incorporate new, emerging imaging technology into our routine clinical practice? PSMA [prostate-specific membrane antigen] PETs [positron emission tomography scans] are obviously very interesting, but they’re expensive and they’re not yet covered in this country. So the reality is, you can actually change management and follow patients when you are using imaging technology that may be able to detect things that we didn’t think patients had before. I think the question remains, again, when you’re looking into the timing of treatment, would identifying disease earlier change my treatment, and therefore change the outcomes of our patients? Or are we simply moving the natural history earlier just by virtue of finding disease with new, novel technology?

Transcript edited for clarity.
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