New-generation androgen receptor signaling inhibitors (ARSIs) in metastatic hormone-sensitive prostate cancer (mHSPC): pharmacokinetics, drug-drug interactions (DDIs), and clinical impact.

INTRODUCTION:The therapeutic scenario of metastatic hormone-sensitive prostate cancer (mHSPC) has dramatically changed in recent years, with the approval of new-generation Androgen Receptor Signaling Inhibitors (ARSIs), in combination with the androgen deprivation therapy (ADT), which was the previous standard of care. Despite showing a similar clinical efficacy, ARSIs, all of which are administered orally, are different in terms of pharmacokinetic and drug-drug interactions (DDIs). AREAS COVERED:This review covers the main pharmacokinetic characteristics of ARSIs that have been approved for the first-line therapy of mHSPC patients, underlying the differences among these molecules and focusing on the known or possible interactions with other drugs. Full-text articles and abstracts were searched in PubMed. EXPERT OPINION:Since prostate cancer occurs mainly in older age, comorbidities and the consequent polypharmacy increase the DDI risk in mHSPC patients who are candidates for ARSI. Waiting for new therapeutic options, in the absence of direct comparisons, pharmacokinetic knowledge is essential to guide clinicians in prescribing ARSI in this setting.