Heterogeneous treatment effects of cabazitaxel in patients with castration-resistant prostate cancer

Prostate cancer is the second most frequent cancer in men worldwide in 2018 representing 7.1% of total diagnosed cancer. Prostate cancer needs testosterone to grow. So, treatment aims to cut off the supply of this male sex hormone, most of which is made by the testicles, and is referred to as medical castration. However, when the cancer continues to grow, this is called castration-resistant prostate cancer (CRPC), which becomes metastatic CRPC (mCRPC) when it spreads to other parts of the body, representing its deadly form. A previous study, the TROPIC trial, demonstrated that a drug called cabazitaxel, when given at a higher dose of 25 mg/m2 (referred to as C25), can extend the lives of patients more effectively than another drug called mitoxantrone in mCRPC. Another study, the PROSELICA trial, compared a lower dose of 20 mg/ m2 of cabazitaxel (C20) with the higher dose. It found that the lower dose was nearly as effective in extending life but with fewer severe side effects. Interestingly, the lower dose seemed to work just as well for most patients, but the higher dose might be better for certain groups of patients. To learn more about this, we will investigate how the treatment effects of cabazitaxel (C25 versus C20) vary among different groups of patients based on data from the PROSELICA (Cabazitaxel at 20 mg/m² Compared to 25 mg/m² With Prednisone for the Treatment of Metastatic Castration Resistant Prostate Cancer) and TROPIC (Cabazitaxel Plus Prednisone Compared to Mitoxantrone Plus Prednisone in Hormone Refractory Metastatic Prostate Cancer) trials. We want to understand how different doses of cabazitaxel (C25 and C20) work for different patients. We will use data from these two previous studies and look at this in two ways. First, we will use a risk-based approach where we group patients based on their risk of poor outcomes. This helps us see if the treatment works differently for high-risk versus low-risk patients. Second, we will use an effect-based approach where we predict how well the treatment might work for each patient based on their characteristics. Overall, this research contributes to refining cancer treatment protocols, aligning with the broader goals of personalized medicine and improving survival for patients with mCRPC treated with cabazitaxel.