Hot flashes are a common side effect reported by men receiving androgen-deprivation therapy (ADT) for the treatment of prostate cancer. We sought to determine whether oxybutynin could improve hot flash symptoms in men with prostate cancer.
Patients with prostate cancer receiving a stable regimen of ADT with least 28 hot flashes per week were randomly assigned to receive either oxybutynin 2.5 mg twice daily, oxybutynin 5 mg twice daily, or matching placebo for 6 weeks. The primary end point was the change in patient-reported hot flash scores since baseline 6 weeks. Additional outcomes included incidence of adverse events (AEs), changes since baseline in Hot Flash–Related Daily Interference Scale (HFRDIS) scores, and patient-reported symptoms.
Eighty-eight patients were enrolled, with the 81 participants eligible for final analysis reporting an average of 10.1 (standard deviation [SD], 5.55) hot flashes per day and an average daily hot flash score of 18.2 (SD, 13.5) included in final analysis. On average, patients on the placebo arm, 2.5 mg oxybutynin arm, and 5 mg oxybutynin arm had reductions in hot flashes/day of 2.15, 4.77 (P = .02), and 6.89 (P < .001), respectively. Daily hot flash scores for placebo, 2.5 mg oxybutynin, and 5 mg oxybutynin reduced by an average of 4.85, 9.94 (P = .07), and 13.95 (P = .002) points, respectively. No treatment-related grade 3+ AEs occurred. HFRDIS total scores improved by 14.2 and 20.7 points in the 2.5 mg (P = .042) and 5 mg (P < .01) oxybutynin arms, respectively, compared with a 3.1-point improvement with placebo.
Oxybutynin is superior to a placebo for the management of ADT-associated hot flashes in men with prostate cancer.
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.
Moving PARP inhibition earlier into the hormone-sensitive androgen pathway modulation–sensitive (APMS) setting, this trial shows talazoparib plus enzalutamide cuts the risk of progression or death in half (HR 0.48) in HRR-altered metastatic prostate cancer, with an impressive 3-year progression-free survival (PFS) of 77% versus 56%. The benefit extends beyond BRCA1/2 to ATM and CDK12 as well, which is clinically meaningful given that two-thirds of this population was non-BRCA.
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.