Real-World Evidence of Triplet Therapy in Metastatic Hormone-Sensitive Prostate Cancer: An Austrian Multicenter Study

The implementation of triplet therapy, consisting of androgen deprivation therapy (ADT), androgen pathway inhibitor (ARPI) and chemotherapy, recently changes the treatment regimens in metastatic hormone-sensitive prostate cancer (mHSPC). Here, we present real-world clinical data on the performance and tolerability in 97 Austrian patients. Among our broad and variable patients collective we show great response rates combined with an acceptable tolerability. Furthermore, we show that treatment was not started simultaneously in 44.8% of patients which was associated with worse response rates. Starting ARPI before chemotherapy was associated with significant higher probability for progression ( P = .023, HR 15.781) than vice versa. 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), thus changing treatment strategies in metastatic hormonesensitive prostate cancer (mHSPC). Patients and Methods: We conducted the first real -world analysis comprising 97 mHSPC patients from 16 Austrian medical centers, among them 79.4% of patients received abiraterone and 17.5% darolutamide treatment. Baseline characteristics and clinical parameters dur ing tr iplet therapy were documented. Mann -Whitney U test for continuous or X 2 -test for categor ical var iables was used. Variables on progression were tested using logistic regression analysis and tabulated as hazard ratios (HR), 95% confidence interval (CI). Results: Of 83.5% patients with synchronous and 16.5% with metachronous disease were included. 83.5% had 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 nonsimultaneous onset of chemotherapy and ARPI, performed in 44.3% of patients, was associated with significantly worse treatment response ( P = .015, HR 0.245). Starting ARPI before chemotherapy was associated with significantly higher probability for progression ( P = .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 to 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 pr imar ily for synchronous high -volume mHSPC. Regardless of selected therapy regimen, treatment is highly effective and tolerable. Preferably therapy should be administered simultaneously, however if not possible, chemotherapy should be started first.