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Announcer:
You’re listening to Project Oncology on ReachMD.  On this episode, we’ll hear from Dr. Jessica Hawley, who’s a medical oncologist at Fred Hutch Cancer Center and an Assistant Professor in the Division of Hematology and Oncology at the University of Washington School of Medicine. Today, she’ll be discussing guideline updates for prostate cancer, which was the topic of her session at the 2024 American Society of Clinical Oncology Genitourinary Cancer Symposium. Let’s hear from Dr. Hawley now.

Dr. Hawley:
This year, at GU ASCO, I’ll be presenting on the NCCN practice-changing guideline updates.  So, what that means is I’ll be discussing the top three biggest changes to the NCCN guidelines for treatment of patients with prostate cancer, the first of which is the expanded use of abiraterone acetate in combination with prednisone for men in the localized disease setting, so those are men with localized very high-risk or node-positive localized prostate cancer who are pursuing radiation therapy as their primary management. Then I shift into the later stages of disease, the castrate-resistant setting, where the NCCN guidelines have updated since last year the use of talazoparib in combination with enzalutamide, and that recommendation comes from the TALAPRO-2 phase III study. And then, finally, I shift to the topic of targeted radioligand therapies and future directions. And though the drug Pluvicto has been in the NCCN guidelines for a few different iterations already, there’s some data that’s been released suggesting that it may be approved in the earlier pre-chemotherapy setting, so the disclaimer there is that it’s not yet in the NCCN guidelines or approved by the FDA in the pre-chemo setting, but it’s something to keep a very close eye on because it may be coming soon. 

Abiraterone acetate is a drug that has been approved in later stages of disease in the castrate-resistant setting both post and pre-chemotherapy and then up in the hormone-sensitive setting, in the metastatic disease setting, and so now what we’re seeing is continuation of that migration of the drug showing effectiveness in earlier stages of the disease. So, in the STAMPEDE data set, the investigators showed that there was significant improval in both six-year metastasis-free survival and overall survival when patients were treated with hormone therapy, meaning the backbone of androgen-deprivation therapy, in combination with the abiraterone acetate compared to patients who received just ADT alone with radiation therapy. 

I think anytime we see patients who have localized disease but meet the criteria that was set out in the STAMPEDE trial—that includes patients having lymph node-positive disease or at least two of the following high-risk features, be it tumor stage T3 or 4 or grade group four or five or a PSA greater than or equal to 40—we should really be counseling our patients on the addition or intensification of their hormone therapy with abiraterone acetate plus prednisone for an extended two-year course.

And in regards to patients who have a homologous recombination repair mutation, there’s now three different drug combinations that are approved by the FDA, and we saw this earlier data from the MAGNITUDE and PROPEL study, which led to FDA approvals of niraparib with abiraterone and prednisone and olaparib with abiraterone acetate and prednisone, but those FDA labels were for—specifically for patients who had BRCA1 and 2 mutations in the setting of metastatic CRPC. And here with TALAPRO-2 we see an expanded FDA label, so it includes the combination of talazoparib and enzalutamide is appropriate for patients both with BRCA1 and 2, but also, the FDA label encompasses other HRR mutations. 

The NCCN goes on to further subdivide its recommendation by applying different categories of recommendation, but talazoparib plus enzalutamide in patients with metastatic CRPC is a category 1 indication if there’s been no prior docetaxel or prior novel hormonal therapy treatment in the CRPC setting, and then that same combination is a category 2A recommendation if their patient had been previously treated with docetaxel but not prior novel hormonal therapy.  And then in the setting of patients who have received prior NHT without docetaxel, this is a category 2B recommendation, meaning that it’s controversial, but that comes from the fact that the benefit over PARP inhibitors alone was not felt to be demonstrated in the TALAPRO-2 study, but the NCCN does caveat it saying that responses are likely.

Announcer:
That was Dr. Jessica Hawley discussing updated guidelines for prostate cancer. To access this episode and others in our series, visit Project Oncology on ReachMD.com where you can Be Part of the Knowledge. Thanks for listening.