LAST WEEK TODAY!

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

Hi fellow warriors! Made it again this week! A small collection of interesting studies, as we wait for ESMO 2025 this coming fall. Stay strong and fight on!

As usual, we also have a podcast if you prefer to listen to the newsletter, you can find it HERE. For more details on everything I talk about here, you can always visit ProstateWarriors.com.​

Clinical Research

• Final Data From Phase 3 PSMAfore Trial About 177Lu-PSMA-617 (Pluvicto)​
  The PSMAfore trial, a phase 3 study, compared 177Lu-PSMA-617 (Pluvicto) to a switch in androgen receptor pathway inhibitor (ARPI) therapy in 468 men with metastatic castration-resistant prostate cancer (mCRPC) who had progressed on one ARPI and had not received taxane chemotherapy. The primary endpoint, radiographic progression-free survival (rPFS), showed a 59% reduction in the risk of progression with 177Lu-PSMA-617. Although the median overall survival (OS) was not significantly different (24.48 months for Pluvicto vs. 23.13 months for ARPI), this may be attributed to 60.3% of ARPI patients crossing over to receive Pluvicto after progression. An adjusted analysis for crossover suggested a potential OS benefit (HR 0.59). The therapy also demonstrated a higher objective response rate (50.7% vs. 14.9%) and improved quality of life, including delayed onset of pain and functional decline. The treatment showed a favorable safety profile with no new safety concerns.
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• Fracture Risk in Prostate Cancer: Insights from a STAMPEDE Trial Analysis​
  A secondary analysis of the STAMPEDE phase 3 trialrevealed a high incidence of fractures in men with high-risk localized or metastatic hormone-sensitive prostate cancer (mHSPC) undergoing androgen deprivation therapy (ADT). Among non-metastatic patients receiving ADT alone, the 5-year cumulative incidence of fracture-related hospitalizations was 11%, rising to 26% at 10 years. In metastatic (M1) patients, the 5-year incidence reached 23%. Zoledronic acid significantly reduced fracture risk in M1 patients (HR 0.73) by inhibiting osteoclast-mediated bone resorption and stabilizing bones affected by ADT and metastases. However, no significant benefit was observed in non-metastatic (M0) patients. Docetaxel showed no clear impact on fracture risk in either group, and no interaction was identified between docetaxel and zoledronic acid. These results support the routine use of zoledronic acid in M1 patients to reduce fracture risk.
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• Low-Dose Abiraterone Acetate Phase 1 Trial Results​
  A phase 1 trial investigated a model-informed 500 mg daily dose of abiraterone acetate (AA) taken with a low-fat meal, aiming to match the efficacy and safety of the standard 1000 mg fasted dose at a lower cost. The rationale stems from AA’s increased bioavailability when taken with food. The trial enrolled nine Asian men with metastatic prostate cancer, all of whom showed a PSA decline by week 12, with 78% achieving a ≥50% PSA reduction. Among six mHSPC patients, a ≥50% decline was seen by week 4, deepening to ≥80% by week 12. The treatment was well tolerated, with hypokalemia being the most common adverse event. Pharmacokinetic and pharmacodynamic modeling confirmed that CYP17A1 enzyme occupancy remained above 80%, despite a 50% reduction in systemic exposure compared to the standard dose—indicating effective endocrine suppression. The safety profile was similar to or better than historical 1000 mg data.
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Preclinical Research

• Understanding and Targeting Neuroendocrine Prostate Cancer​
  Researchers at Emory University have uncovered the genetic and epigenetic mechanisms that drive neuroendocrine prostate cancer (NEPC), a lethal subtype that affects roughly 20% of advanced prostate cancer cases. The study identified a progressive reprogramming of chromatin structure, orchestrated by the transcription factors FOXA2 and NKX2-1, which activate gene networks leading to a neuroendocrine identity. Unlike typical prostate cancer, NEPC is aggressive and resistant to hormone therapy. The team successfully blocked this transformation in lab and animal models by targeting the epigenetic regulators CBP and p300 with CCS1477, a drug currently in early-phase trials.
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• Novel Immunotherapy to Target Solid Tumors​
  A new immunotherapy is in development to make all solid tumors, including typically resistant ones like prostate cancer, vulnerable to immune attack. The approach reprograms tumors to express a synthetic, non-human antigen on their surface, which immune cells can recognize and destroy. This is achieved by delivering genetic instructions via an engineered viral vector directly into the tumor, prompting cells to express the synthetic marker. Custom-designed CAR-T cells, trained to target this antigen, are then introduced to eliminate the marked cancer cells. This tumor-agnostic approach bypasses the need for native tumor-specific antigens and reshapes the tumor microenvironment to become more responsive to immune activity. Clinical trials are expected to begin in 2026.
• Cancer-Fighting Potential of Cyproheptadine
  A Taiwanese research team has found that cyproheptadine, the active compound in the antihistamine Periactin, may enhance the immune system’s ability to fight cancer. Over six years, the team observed that cyproheptadine suppresses bladder tumor growth and improves the immune microenvironment. The drug regulates epigenetic activity in cancer cells, increasing the expression of immune recognition markers and enhancing their visibility to natural killer (NK) cells. In mouse models, it slowed tumor progression and increased NK cell infiltration. With an established safety record, cyproheptadine shows promise for repurposing as an immunotherapy, particularly for bladder cancer, with potential applications in other difficult-to-treat tumors.​
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And…that’s all folks! For today at least!
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Have a great weekend!

Max