Cardiovascular Risk and Prostate Cancer Management - Episode 4

An Overview of the Prostate Cancer Treatment Landscape

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A comprehensive review of the therapeutic classes available for patients with prostate cancer.


Bhavesh Shah, RPh, BCOP: Obviously, we know that there are numerous androgen deprivation [ADT] therapies that patients can be on for prostate cancer. This includes neoadjuvant, adjuvant, or even concurrent androgen deprivation therapy. Then moving to patients who may have metastatic hormone-sensitive prostate cancer or nonmetastatic castration-resistant prostate cancer, these patients will essentially be on androgen deprivation therapy that includes either a GnRH [gonadotropin-releasing hormone] agonist or a GnRH antagonist. Those are the 2 different modalities. Essentially there are 3 LHRH [luteinizing hormone-releasing hormone] agonists. One is leuprolide, the second is goserelin, and third is triptorelin, all injectable. Leuprolide can be given subcutaneously or IM [intramuscularly], depending on the formulation that you’re using.

Then the GnRH antagonists, there are 2, one that’s injectable, degarelix, and then the second one, which was approved recently, it’s called relugolix, which is an oral GnRH antagonist. Until this day, we did not have an oral GnRH antagonist, which is a huge game-changer in this patient population. They don’t have to come in for frequent injections [at] the clinic, they could be taking oral drug at home. It’s a different mechanism from your LHRH agonist, which is not the same as your GnRH antagonist, which directly suppresses testosterone. The LHRH agonists are a negative feedback mechanism, where essentially you increase the concentrations and then there is a negative feedback loop mechanism, which suppresses the production of it afterward. Those are the main treatments that are used in prostate cancer. You can see that it can be used across the continuum of the disease, so patients are really never off of these therapies.

Maria Lopes, MD, MS: It’s certainly an exciting time for prostate cancer with all the new therapeutic options that are emerging. We’ve had ADT for decades, but now there are oral ADTs, alternatives to the injectable Lupron [leuprolide acetate for injection], noninferior to GnRH antagonists. These agents promise some innovation with faster recovery of testosterone. But what appears to be quite interesting is that the cardiovascular [CV] events appear to be significantly lower vs the traditional GnRH agonists, with as much as a 54% decrease in CV events compared to leuprolide. Some of the MACE [major adverse cardiac events] end points also reflect this lower cardiac risk, with the odds ratio being significantly less in terms of cardiovascular events vs leuprolide. What’s also interesting as you look at other data, the HERO trial, there appears to be significant separation of these cardiac risk events within a matter of weeks. So it’s interesting, as we learn more about clinical differentiation, but also the impact for a lot of these men, given that they may already have significant cardiovascular disease risks, compounding that with ADT, and maybe safer alternatives that can be used to reduce that risk becomes really important.

Other agents that are very much now part of the management and are included in NCCN [National Comprehensive Cancer Network] guidelines include the PARP inhibitors, and the importance of genetic testing and family history in determining if you qualify for these agents. These include olaparib as well as rucaparib if you have certain diagnostic markers. With rucaparib, the marker is BRCA1/2, used in metastatic castration-resistant prostate cancer. With olaparib, a trial showed significant benefit over abiraterone or enzalutamide with increasing both PFS [progression-free survival] as well as OS [overall survival]. These are now really important considerations in the management of prostate cancer.

On the nonmetastatic castrate resistant prostate cancer front, there are also some significant advances with studies like SPARTAN, ARAMIS, PROSPER, which really have demonstrated the benefit of apalutamide, darolutamide, as well as enzalutamide in combination with ADTs to prolong PFS as well as improve overall survival. So, early identification and combination therapies are certainly impacting overall survival and are important considerations.

Finally, there are some very innovative targeted treatments to PSMA [prostate-specific membrane antigen], radionuclides, which destroy cancer cells with something called lutetium-177 that are promising for potential future therapies in metastatic castration-resistant prostate cancer. So a lot of options are emerging, very innovative, some involving genetics. It’s becoming more and more about patient segmentation, and emphasizing the need for both patient education as well as maybe even provider education in terms of helping patients understand the treatment options and the risks and benefits.

Transcript edited for clarity.