A drug-drug interaction study found that apalutamide induces an enzyme (CYP3A4) that lowers relagolix concentrations, leading to suboptimal hormonal suppression. To maintain efficacy when used in combination, the standard dose of the oral GnRH antagonist relagolix must be doubled.
The term "castration sensitive or resistant" is being phased out for more patient-centric language. "Androgen pathway modulation" better reflects the biological state, especially as new treatments are used without traditional testosterone-lowering therapy, a shift recommended by the Prostate Cancer Working Group 4.
While the landmark EMBARK study enrolled patients with no metastatic disease on conventional imaging (CT/bone scan), a similar population scanned with advanced PSMA PET imaging showed 84% had M1 disease. This suggests that treatments for this population are effective against micrometastases not visible on older scans, blurring the lines between localized and metastatic states.
The CAPITELLO-281 trial showed the AKT inhibitor capivasertib delayed disease progression in PTEN-deficient prostate cancer. However, without a demonstrated overall survival benefit yet, its path to becoming a new standard of care is uncertain. This highlights the growing debate over whether delaying progression is a sufficient endpoint to justify added toxicities when survival isn't improved.
The ERA SAFE study found that a bi-weekly, lower-dose docetaxel regimen for triplet therapy significantly lowers grade 3-4 adverse events compared to the standard 3-week schedule. It reduced the risk of neutropenic fever from 5.5% to 1.7% while maintaining similar efficacy, offering a safer alternative for frail or vulnerable patients.