LAST WEEK TODAY!

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

Hello fellow warriors! This week we have a solid set of clinical trials and retrospective studies. We are making progress day by day.
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.​

Clinical Research

• Phase 3 Trial: PSMAddition Reports Positive Outcomes for mHSPC
  ​The PSMAddition trial compared the addition of lutetium-177 PSMA (Pluvicto) to standard androgen deprivation therapy (ADT) and an androgen receptor pathway inhibitor (ARPI) in men with metastatic hormone-sensitive prostate cancer (mHSPC). Results showed a 58% lower risk of PSA progression and a 28% lower risk of radiographic progression or death in the combination arm compared to standard care alone. Deep biochemical responses were more frequent with the triplet therapy, as 87% of patients reached a PSA below 0.2 ng/mL at 48 weeks. While overall survival data are not yet mature, the addition of Pluvicto significantly improved disease control and radiographic progression-free survival.​
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• Phase 2 Trial: A-DREAM Evaluates Therapy Interruption in mHSPC
  ​The A-DREAM / Alliance A032101 trial investigated whether men with mHSPC who achieve an exceptional response to ADT and an ARPI can safely stop treatment. Participants had to reach a PSA below 0.2 ng/mL and maintain it for a specific duration before interrupting therapy. The study successfully met its primary endpoint, with 41% of participants remaining off treatment and recovering normal testosterone levels 18 months after interruption. Overall, 58% of patients remained treatment-free at the 18-month mark, suggesting that a subset of high-responding patients may benefit from meaningful breaks in hormonal therapy to reduce toxicity.​
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• Phase 2 Trial: ARACOG Shows Cognitive Benefit of Darolutamide
  ​The ARACOG trial provided the first prospective, head-to-head randomized comparison of the cognitive effects of darolutamide versus enzalutamide in a US population. Over 24 weeks, enzalutamide was associated with a significantly greater decline in objective cognitive performance across domains like executive function and memory. Conversely, patients on darolutamide showed evidence of a learning effect on repeated testing, which was likely offset by treatment-related impairment in the enzalutamide group. These findings highlight darolutamide as a potentially better option for patients where maintaining quality of life and cognitive function is a primary concern.​
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• Phase 2 Trial: BAT as an Immune Primer for Sipuleucel-T
  ​This study explored using bipolar androgen therapy (BAT) as a sequencing strategy before sipuleucel-T to enhance immune responses in men with mCRPC. While historical data for sipuleucel-T shows a roughly 50% immune response rate, 100% of the evaluable patients in this trial became ELISPOT-positive, and T-cell proliferation responses also reached 100%. The results suggest that BAT may prime the tumor and immune environment, allowing the immunotherapy to work more consistently. However, because this was a single-arm study, a randomized trial is needed to definitively confirm that BAT is responsible for this potentiation.​
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• Phase 2 Trial: CONVERGE-01 Evaluates CONV01-α After Pluvicto
  ​The CONVERGE-01 trial is testing actinium-225 rosopatamab tetraxetan (CONV01-α), a targeted alpha radioligand therapy, in patients with mCRPC who previously received lutetium-177 PSMA. Unlike other agents, CONV01-α uses a monoclonal antibody to deliver a potent alpha emitter, potentially enabling highly localized DNA damage in PSMA-expressing cells. Among patients treated at the recommended dose, 45.4% achieved at least a 50% PSA decline, including some who were previously refractory to Pluvicto. The safety profile was considered manageable, with limited hematologic and salivary toxicity.​​
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• Phase 2 Trial: TALENT Explores Talazoparib in HRR-deficient mCRPC
  ​The TALENT trial is evaluating the efficacy of adding enzalutamide to talazoparib monotherapy in men with HRR-deficient mCRPC who have progressed specifically after abiraterone. The trial seeks to determine if the synergy between PARP and AR inhibition remains effective in a population that has already developed resistance to androgen-biosynthesis inhibitors. Notably, the study limits patients with ATM mutations to 15% of the population to ensure that results are not skewed by tumors that may respond differently to PARP inhibitors compared to those with BRCA1/2 mutations. This trial aims to refine which molecular subtypes derive the greatest benefit from this dual inhibition strategy.​
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• Phase 1 Trial: ABBV-969 Shows Robust Responses in Pretreated mCRPC
  ABBV-969 is a first-in-class, dual-targeting antibody-drug conjugate (ADC) designed to target both PSMA and STEAP1. In a dose-escalation trial involving heavily pretreated mCRPC patients (median of five prior therapies), the drug demonstrated significant antitumor activity. At doses of 3 mg/kg and higher, 67% of patients achieved a PSA50 response, and the confirmed objective response rate reached 45%. By targeting two different antigens, ABBV-969 may better address tumor heterogeneity and reduce the risk of antigen escape.​
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• Phase 1 Trial: HRS-5041 Targets AR Mutations in Prostate Cancer
  HRS-5041 is an oral androgen receptor degrader designed to eliminate both wild-type and mutant forms of the receptor. In a phase 1 trial of 156 patients, the drug showed differential activity based on AR mutation status, with higher response rates in those harboring AR-LBD mutations. For patients with these mutations, PSA50 response rates reached 48.4%, and the 8-month radiographic progression-free survival rate was as high as 85.3%. The treatment was generally well tolerated, with no dose-limiting toxicities observed even at the highest explored doses.​

Preclinical Research & Reviews

• ARPI Doublet vs Triplet Therapy and the Role of PSA Nadir
  ​A large real-world study compared ARPI doublets (ADT + ARPI), docetaxel doublets, and triplet therapy (ADT + ARPI + docetaxel) in patients with metastatic prostate cancer. While clinicians often reserved triplets for higher-risk patients, ARPI doublets were associated with a significantly longer median overall survival of 109 months, compared to 79 months for triplets. Note: the difference reflects also the fact that triplet therapy is generally used in patients with the worst prognoses.
  A PSA nadir below 0.2 ng/mL served as a powerful prognostic marker across all groups; those who reached this deep response with an ARPI doublet had an extraordinarily long median survival of 202 months, the triplet had a median survival of 128 months. These results underscore that biochemical response depth is a critical indicator of long-term prognosis regardless of the specific treatment regimen used.​
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• CT-Measured Muscle Quality Predicts Survival in nmCRPC
  ​Research from Japan suggests that muscle quality, characterized by fat infiltration, is a better predictor of survival in non-metastatic castration-resistant prostate cancer (nmCRPC) than muscle size. The study used CT scans to measure intramuscular adipose tissue content (IMAC), finding that patients with poorer muscle quality had an 80% higher risk of death. While lower muscle quantity also correlated with shorter survival in simple analyses, it was not an independent predictor once adjusted for factors like age and comorbidities. Although muscle quality does not appear to impact drug response or safety, it may help clinicians refine prognosis and discuss lifestyle interventions like nutrition and exercise.​
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• Real-World Evidence on Abiraterone vs Darolutamide in mHSPC
  ​A retrospective analysis using the TriNetX database compared outcomes for patients with hormone-sensitive disease treated with either abiraterone or darolutamide. The data indicated that patients on abiraterone had a significantly higher rate of progression to hormone-resistant disease (23.8% vs 9.1%) and a higher all-cause mortality rate compared to those on darolutamide. While abiraterone patients had a median overall survival of 60 months, the median was not reached in the darolutamide group during the study period. These results are hypothesis-generating and suggest a potential survival advantage for darolutamide, though prospective randomized trials are needed for confirmation.
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• When Scans Stay Stable: rPFS as a Reflection of Overall Survival
  ​A post-hoc analysis of the TALAPRO-2 trial presented at the 2026 AUA Meeting confirmed that radiographic progression-free survival (rPFS) is a strong surrogate for overall survival in mCRPC. The correlation between these two endpoints was found to be moderate to strong (0.7 to 0.82) across various subgroups, including those with and without HRR or BRCA mutations. This consistency gives clinicians more confidence in using imaging-based results to guide therapy. For regulators, the strong correlation supports the use of rPFS as a primary endpoint in clinical trials, potentially speeding up the approval of new treatments by several years.​

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And…that’s all folks! For today at least!
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Have a great weekend!

Max