Real-world evidence of triplet therapy in metastatic hormone-sensitive prostate cancer - an Austrian multicenter study

Introduction Two randomized trials demonstrated a survival benefit of triplet therapy (androgen deprivation therapy [ADT]) plus androgen receptor pathway inhibitor [ARPI] plus docetaxel) over doublet therapy (ADT plus docetaxel) changing treatment strategies in metastatic hormone-sensitive prostate cancer (mHSPC). Patients and methods We conducted the first real-world analysis including 97 mHSPC patients from sixteen Austrian medical centers. 79.4% of patients received abiraterone, 17.5% darolutamide, 2.1% apalutamide and 1% enzalutamide. Baseline characteristics and clinical parameters during triplet therapy were documented. Mann-Whitney-U-Test for continuous or X²-test for categorical variables was used. Variables on progression were tested using logistic regression analysis and tabulated as hazard ratios (HR), 95% confidence interval (CI). Results 83.5% of patients with synchronous and 16.5% with metachronous disease were included, with 83.5% high-volume disease diagnosed by conventional imaging (48.9%) or PSMA PET-CT (51.1%). While docetaxel and ARPI were administered consistent with pivotal trials, prednisolone, prophylactic gCSF and osteoprotective agents were not applied guideline conform in 32.5%, 37% and 24.3% of patients, respectively. Importantly, a non-simultaneous onset of chemotherapy and ARPI, performed in 44.8% of patients, was significantly associated with worse treatment response (p=0.015, HR 0.245). Starting ARPI before chemotherapy was associated with significant higher probability for progression (p=0.023, HR 15.781) than vice versa. Strikingly, 15.6% (abiraterone) and 25.5% (darolutamide) low-volume patients as well as 14.4% (abiraterone) and 17.6% (darolutamide) metachronous patients received triplet therapy. Adverse events (AE) occurred in 61.9% with grade 3-5 in 15% of patient without age-related differences. All patients achieved a PSA decline of 99% and imaging response was confirmed in 88% of abiraterone and 75% of darolutamide patients. Conclusions Triplet therapy arrived in clinical practice primarily for synchronous high-volume mHSPC. Regardless of selected therapy regimen, treatment is highly effective and tolerable. Preferably therapy should start simultaneously, if not possible chemotherapy should be started first. Take Home Massages Triplet therapy consisting of ADT plus ARPI (abiraterone or darolutamide) plus docetaxel is an effective and mostly well tolerable treatment option for mHSPC patients also in the real-world setting especially for synchronous, high-volume patients.