A previous trial involving patients with metastatic prostate cancer that was resistant to androgen pathway modulation (formerly referred to as castration-resistant) showed that adding talazoparib to enzalutamide significantly improved imaging-based progression-free survival and overall survival, with the greatest benefit observed in the cohort with alterations in homologous recombination repair genes.
In this ongoing, phase 3, double-blind trial assessing talazoparib in patients with metastatic androgen pathway modulation–sensitive [APMS] prostate cancer harboring alterations in homologous recombination repair genes, we randomly assigned patients in a 1:1 ratio to receive talazoparib a dose of 0.5 mg plus enzalutamide a dose of 160 mg once daily (talazoparib group) or placebo plus enzalutamide a dose of 160 mg once daily (control group). Randomization was stratified according to disease status (new or relapsed), disease volume (high or low), and BRCA (vs. non-BRCA) mutation status. The primary end point was investigator-assessed imaging-based progression-free survival. The key secondary end point was overall survival.
A total of 300 patients were assigned to the talazoparib group and 299 to the control group. 3 years, progression-free survival was 77% in the talazoparib group and 56% in the control group (hazard ratio for disease progression or death, 0.48; 95% confidence interval [CI], 0.36 to 0.65; P
Talazoparib added to enzalutamide led to significantly better imaging-based progression-free survival than placebo plus enzalutamide among patients with metastatic APMS prostate cancer harboring alterations in homologous recombination repair genes. Serious adverse events were more common with talazoparib plus enzalutamide than with placebo plus enzalutamide. (Funded by Pfizer; TALAPRO-3 ClinicalTrials.gov number, NCT04821622.)
Adding olaparib to Radium 223 improve progression-free survival (PFS) in patients with bone mets (median 8.9 v 4.7 month) esp. in those who did not receive prior taxotere.
An important post-hoc analysis from ARCHES and PROSPER that quantifies something we've suspected clinically, roughly 1 in 4 enzalutamide-treated patients who progress radiographically have no prostate-specific antigen (PSA) rise, and the majority won't meet PCWG2/3 PSA progression criteria. Liver metastases were 5-fold more common at radiographic progression on enzalutamide versus control, suggesting lineage plasticity and AR-independent clones are the culprit. Bottom line for practice: don't wait for PSA to rise before imaging your metastatic hormone-sensitive prostate cancer (mHSPC) and nonmetastatic castration-resistant prostate cancer (nmCRPC) patients on ARPIs, periodic cross-sectional imaging, especially in the first two years, is warranted regardless of PSA trend.
Solid pragmatic phase II showing oxybutynin 2.5mg and 5mg BID (twice a day) both beat placebo for hot flash reduction in men on androgen-deprivation therapy (ADT), with no serious toxicities beyond expected dry mouth. Given that venlafaxine failed in this population and megestrol/medroxyprogesterone carry real concerns, this gives us an evidence-based option we can feel good about reaching for, especially in patients who also have urinary symptoms. Neurokinin B (NKB) antagonists are coming but not yet studied here, so oxybutynin fills a real gap now.
Overall survival was 78.9% in the combination group compared with 69.5% in the leuprolide-alone group (HR 0.60). Enzalutamide monotherapy resulted in an overall survival of 73.1%, which was not statistically significant. We were already aware of the progression-free survival benefit; now we have overall survival data. This case was also presented in the MOC questions, where the correct answer was to add enzalutamide for a patient with a rising PSA on an LHRH agonist without imaging evidence of disease.
Metformin did not significantly reduce the risk of disease progression compared with active surveillance in patients with low-risk prostate cancer.