In patients who received enzalutamide, we characterized the development of radiographic progression (rPD) without prostate-specific antigen (PSA) rise or progression in metastatic hormone-sensitive prostate cancer (mHSPC) and nonmetastatic castration-resistant prostate cancer (nmCRPC).
We conducted a post hoc analysis in two phase III trials (N = 2,551; ARCHES [ClinicalTrials.gov identifier: NCT02677896]; PROSPER [ClinicalTrials.gov identifier: NCT02003924]) for co-occurrence of rPD ± Prostate Cancer Working Group 2/3-defined PSA progression, and rPD ± any PSA rise from baseline/nadir by treatment. Kaplan-Meier methods were used for overall survival (OS) outcomes.
In ARCHES, 3.5% and 8.5% of 574 patients with mHSPC treated with enzalutamide plus androgen-deprivation therapy (ADT) had no PSA rise or PSA progression rPD, respectively. Of 79 patients with rPD who received enzalutamide plus ADT, 25.3% had no PSA rise and 62.0% did not meet PSA progression criteria compared with 7.4% and 38.3% of 188 patients with rPD treated with ADT alone, respectively. In PROSPER, 4.4% and 10.3% of 933 patients with nmCRPC treated with enzalutamide plus ADT had no PSA rise or PSA progression, respectively, rPD. However, of 187 patients with rPD who received enzalutamide plus ADT, 21.9% had no PSA rise and 51.3% did not meet PSA progression criteria compared with 3.6% and 18.8% of 224 patients treated with placebo/ADT, respectively. Liver metastases were >5-fold higher in enzalutamide-treated patients with rPD events versus control, although sample size was small. Compared with no rPD, enzalutamide-treated patients with rPD ± PSA rise or progression had worse OS.
Given the frequent discordance and poor prognosis of imaging-based progression in the absence of PSA changes during enzalutamide treatment in mHSPC and nmCRPC, periodic surveillance using imaging is recommended.
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.
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.
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.