Xtandi and Talzenna Therapy Shows Responses in Advanced Prostate Cancer

Dr. Chandler Park, a medical oncologist of Genitourinary Medical Oncology, at the Norton Healthcare Institute, in Louisville, Kentucky, sat down for an interview with CURE® to discuss the biggest takeaway from the 2025 Annual ASCO Genitourinary (GU) Cancers Symposium in terms of prostate cancer treatment.

The TALAPRO-2 study, a large phase 3 trial presented at the meeting, evaluated the combination of Xtandi (enzalutamide) and Talzenna (talazoparib) in metastatic castration-resistant prostate cancer, he explained. The investigative agent demonstrated a 20% reduction in cancer progression regardless of BRCA1/BRCA2 mutation status, with potential future FDA approval, according to the expert.

Read more from our interview with Park on additional takeaways from the meeting encompassing bladder and kidney cancer, as well as our conversation with him on the importance of precision medicine in oncology.

Transcript:

[An important] study that is in the prostate cancer field is the TALAPRO-2 study. The [trial looked at] patients with prostate cancer when they're diagnosed. There are two types of prostate cancer: one is called metastatic-hormone sensitive prostate cancer, and that means that these patients are still sensitive to testosterone, so we give them testosterone blockers — kind of like estrogen blockers for patients with breast cancer; but the more aggressive type is called castrate-resistant prostate cancer. This [diagnosis] is very tough and we want to find new treatments for this.

In TALAPRO-2, patients got randomized to Xtandi, which is considered a great standard of care treatment for metastatic castration-resistant prostate cancer, and the other arm received Xtandi plus Talzenna, which is considered a PARP inhibitor. Now, PARP inhibitors are something that we might all hear about when we treat for patients in ovarian cancer, breast cancer and pancreatic cancer, and the key is they need these genetic markers called BRCA1 and BRCA2. It was very similar in the prostate cancer world, where patients had to have either the BRCA1 or BRCA2 mutations; these mutations could be either in the germline or the somatic.

Germline is whenever a buccal swab or blood check [is done] to see if [patients] inherited BRCA1/BRCA2 genes. Now, what's somatic mutation? Imagine if I have a black mark on my hand, and that mark is melanoma. If they take a biopsy of this black part of my hand, and they take a biopsy of my normal hand, the DNA of that cancer is completely different from the skin, and that is called somatic mutation. If there's a BRCA1/BRCA2 mutation inside the cancer, then you could qualify for a PARP inhibitor. Now, with all that said, that is considered a select patient population; we must see if the patients qualify for a PARP inhibitor in this study.

What makes this study, as we considered it, a highlight at ASCO GU, is they didn't look at that in terms of randomizing patients to the study, they took all comers. It was close to 800 patients, a large phase 3 trial, in which patients got randomized to Xtandi versus Xtandi plus Talzenna, and there was a 20% decrease in terms of the cancer.

A lot is based upon the molecular subgroups, but it is encouraging that if a patient shows up with metastatic castration-resistant prostate cancer [we could refer to this]. Although I recommend everybody [complete testing], not everybody practices in the big city. Some people practice in rural America, and they might not have access [to germline and somatic testing]. So if they don't have access, and these oncologists see patients… [they should focus on family history of cancer], as there might be some kind of genetic concern for cancer. In these situations, I would consider this based upon the ASCO GU study. Now, it is not FDA approved yet, but I anticipate it will be, so we'll cross our fingers.

Those are the three impactful studies that I see for patient care [following the ASCO GU Symposium].

Transcript has been edited for clarity and conciseness.

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