Drug-drug interactions in metastatic hormone-sensitive prostate cancer (mHSPC): practical considerations for treating men with androgen receptor pathway inhibitors and common medications in this stage

Abstract

Introduction New androgen receptor pathway inhibitors (ARPIs) are an essential part of the treatment strategy for patients with metastatic hormone-sensitive prostate cancer (mHSPC). Despite the good tolerability of ARPIs, after treatment is started, drug-drug interactions (DDIs) between these and other medications frequently taken by these patients may appear. DDIs may reduce the therapeutic effect of both and lead to increased adverse events. DDIs should be carefully assessed before an ARPI is started.

Areas covered We first review the current therapeutic landscape for mHSPC, common age-related comorbidities and other comorbidities or adverse events arising from previous or current treatments for prostate cancer, and patients’ symptomatology. We then analyze the potential toxicities arising from medications for these conditions and those of mHSPC: ARPIs (abiraterone acetate plus prednisone/prednisolone, enzalutamide, apalutamide, and darolutamide) and docetaxel.

Expert opinion Before mHSPC patients are treated with an ARPI, careful assessment of patient eligibility for each treatment alternative and potential DDIs between these and treatments for current comorbidities is a fundamental component in clinical decision-making. ARPIs with low potential DDIs allow keeping current concomitant medications without significant relevant dose adjustments and help reduce the risk of toxicities and comorbidity-related decompensation.

Plain Language Summary Prostate cancer is one of the most common cancers in men, especially those aged 60 years old or older. Many of these men are also taking medicines for other health problems such as high blood pressure, diabetes, high cholesterol, or other age-related or unrelated conditions. Androgen deprivation therapy (ADT) is a treatment used in prostate cancer when the first treatment options with curative intent have failed. This treatment lowers the level of androgens, male hormones that make the cancer grow. Over time, ADT may not be enough to keep prostate cancer under control. This is when it spreads to the body, causing ‘metastases.’ This stage of prostate cancer is known as ‘metastatic hormone-sensitive prostate cancer,’ which means that it is still sensitive to the effect of ADT. If not treated, it may lose this sensitivity and become ‘castration-resistant.’ This stage of the disease is lethal.

New drugs called ‘androgen receptor pathway inhibitors’ (ARPIs), such as abiraterone, enzalutamide, apalutamide, and darolutamide help ADT to better control prostate cancer. The problem is that the way ARPIs work in the body may interfere with the ways other medications taken by the patient work and vice versa. This is called a ‘drug-drug interaction’. Consequently, all these medications do not work as they should, or even worse, they can cause unexpected side effects. Before starting an ARPI, healthcare professionals should carefully check all the medications the patient is taking.

Choosing an ARPI with fewer interactions can help ensure the patient’s other health conditions are well-managed and that the ARPI will work well. This is important to keep patients as healthy and safe as possible while they are being treated for prostate cancer.