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

Abstract

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 chi-square-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.