LAST WEEK TODAY!

A summary of what was published on ProstateWarriors.com during the past week

Hi fellow warriors! This time, I welcome you with a haunting photo from the Venice Carnival, which has just begun.

As many of you know, last week was ASCO GU 2025, and there’s a lot to cover. I’ve reviewed around 200 of the 400+ prostate cancer papers presented, focusing on those that might be most relevant for people with advanced prostate cancer (PCa). I’m working on filtering out the key insights to bring you the most useful and impactful findings.

As usual, we also have a podcast if you prefer to listen to the newsletter, you can find it HERE.​

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Clinical Research

• Darolutamide Triplet Therapy for mHSPC
  ​A population-adjusted network analysis confirmed that darolutamide + ADT + docetaxel significantly improves survival in metastatic hormone-sensitive prostate cancer (mHSPC). Using advanced statistical modeling, the study found superior overall survival (OS) compared to abiraterone + ADT ± docetaxel, apalutamide + ADT, and enzalutamide + ADT, reinforcing the triplet therapy’s role as a leading treatment option.
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• CBP-1018 for mCRPC
  ​The investigational bi-ligand–drug conjugate (Bi-XDC), CBP-1018, is showing promising efficacy in metastatic castration-resistant prostate cancer (mCRPC). In a phase I/II trial, the objective response rate (ORR) was 20%, while the disease control rate (DCR) was an impressive 88%. At seven months, 70% of patients remained progression-free, and at 12 months, 60% continued responding positively. Notably, for patients who had prior taxane chemotherapy and ARPI treatments, the seven-month radiographic progression-free survival (rPFS) rate was 66%, demonstrating effectiveness even in heavily pre-treated cases.
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• Talazoparib Plus Enzalutamide for HRR-Deficient mCRPC​
  The Phase 3 TALAPRO-2 trial confirmed the efficacy of talazoparib + enzalutamide as a first-line treatment for HRR-deficient mCRPC. Patients receiving the combination therapy had a median OS of 45.1 months, compared to 31.1 months for enzalutamide alone. The combination also significantly prolonged rPFS to 30.7 months, compared to 12.3 months in the placebo group. The greatest OS benefit was seen in BRCA1/2-mutated patients, reinforcing the importance of genetic testing for treatment selection.
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• Mevrometostat for mCRPC
  ​A Phase I trial of mevrometostat, an EZH2 inhibitor, showed promising results for mCRPC patients previously treated with hormone therapy and chemotherapy. When combined with standard hormone therapy, disease progression rates were reduced by 50%, and the risk of death decreased by 49%. Phase III trials (MEVPRO-1 and MEVPRO-2) are currently ongoing to further evaluate its benefits.
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• Transdermal Estradiol Patches
  ​A Phase 2 STAMPEDE trial suggests that transdermal estradiol (tE2) patches could serve as a safer and equally effective alternative to LHRHa in metastatic prostate cancer when used alongside ARPIs. The PSA response rates were comparable between the two groups, but tE2 patches showed a better safety profile, with fewer hot flashes and lower hypertension rates.
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• Gut Health and Prostate Cancer
  ​A world-first double-blind, placebo-controlled trial showed that improving gut health may slow prostate cancer progression. Men who combined a phytochemical-rich supplement (ginger, cranberry, pomegranate, turmeric, broccoli, and green tea) with a probiotic blend (lactobacillus, inulin, and vitamin D) experienced PSA going from a 21.7% PSA riseÂto a 20% decrease. Additionally, participants reported improved urinary function and sexual health, reinforcing the growing evidence of the gut-prostate axis in cancer progression.
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• BR111 ADC​
  A new antibody-drug conjugate (ADC) therapy, BR111, is emerging as a potential treatment for advanced prostate cancer by targeting ROR1, a protein expressed in aggressive forms of the disease.Preclinical studies indicate that BR111 effectively binds to ROR1-positive tumor cells, delivering a potent cytotoxic payload that induces direct cancer cell death. Additionally, the therapy activates immune-mediated mechanisms, further enhancing its ability to destroy cancer cells.With promising preclinical efficacy, BR111 represents a novel approach in prostate cancer treatment.
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• PSA Nadir as a Predictor of Outcomes​
  A real-world analysis from the IRONMAN registry confirms that achieving an undetectable PSA nadir (<0.2 ng/mL) within the first year of treatment is strongly associated with better outcomes in metastatic hormone-sensitive prostate cancer (mHSPC). Patients who reached this milestone had lower relapse rates and longer disease control. Among treatment regimens, ADT + ARPI resulted in the highest rates of undetectable PSA nadir, reinforcing its effectiveness in achieving deep PSA suppression.
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• HRR Alterations and Their Impact on mHSPC
  ​A recent study evaluated the impact of homologous recombination repair (HRR) alterations (HRRalt) in metastatic hormone-sensitive prostate cancer (mHSPC) and found that patients with these genetic mutations progressed to castration resistance significantly faster (shorter TTCR). However, overall survival (OS) was not significantly affected, except in CDK12-mutated cases, where both TTCR and OS were worse.
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• AI Boosts Prostate Cancer Detection Accuracy​
  The FDA-cleared AI tool,Âis revolutionizing prostate cancer diagnostics with exceptional accuracy. It achieved a 99.6% positive predictive value (PPV) in heatmap analysis and identified 13% of cancer cases initially missed by pathologists. These results highlight AI’s potential to enhance diagnostic precision, reduce errors, and improve early detection, ultimately leading to better patient outcomes.

Preclinical Research

• NSD2 Inhibition for Treatment-Induced Neuroendocrine Prostate Cancer
  ​New research identifies NSD2 as a potential therapeutic target for treatment-induced neuroendocrine prostate cancer (t-NEPC), an aggressive form of the disease that emerges after standard treatments. The selective NSD2 inhibitor, KTX1001, has shown strong anti-tumor effects in both lab studies (in vitro) and animal models (in vivo), suggesting it could be a promising new treatment option.
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• Hyperthermia for Prostate Cancer
  ​Hyperthermia (HT) is emerging as a promising adjuvant therapy that can enhance the effectiveness of immunotherapy (IT) and targeted therapy (TT) in prostate cancer treatment. By heating tumors to 40–44°C using external energy sources, HT disrupts DNA repair pathways, activates the immune system, improves drug delivery, and counteracts hypoxia, making cancer cells more vulnerable to treatment. As research advances, HT could become a valuable addition to standard therapies, offering new hope for improved treatment outcomes.
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And…that’s all folks! For today at least!
Please let me know if there is anything I can improve in my newsletters, and let me know if you have enjoyed the podcast.

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Have a great weekend!

Max