Real-world analysis of efficacy and safety of biweekly gemcitabine and docetaxel (GEMDOC) in heavily pretreated metastatic castration-resistant prostate cancer.

Abstract

e17027 Background: Metastatic castration-resistant prostate cancer (mCRPC) has poor prognosis and median overall survival (OS) of approximately 25 months. Available treatment include chemotherapy, hormonal therapy, immunotherapy, targeted agents, and radiopharmaceuticals. While combination of GEMDOC has demonstrated efficacy in solid tumors, its real-world application in mCRPC remains unclear. This single institute retrospective study evaluates safety and efficacy of biweekly GEMDOC in mCRPC patients treated between 2017 and 2024. Methods: A retrospective analysis was performed on mCRPC patients who had disease progression or were ineligible for all approved standard of care therapies and received biweekly docetaxel (50 mg/m²) and gemcitabine (1500 mg/m²) on a 28-day cycle at Winship Cancer Institute Atlanta, GA. Data collected included baseline characteristics, prior therapies, PSA decline (≥90%, ≥60%, ≥30%), progression-free survival (PFS), OS, and adverse events. Analyses were stratified by ethnicity, smoking status, prior therapies, visceral disease, and de novo presentation. Results: Among 28 patients (median age 72 years), 19 (68%) were White, 9 (32%) were Black. Most (90%) had prior taxane exposure, 29% presented de novo metastatic disease, and 14% had visceral involvement. Patients received 1–5 prior lines of therapy. PSA declines of ≥90%, ≥60%, and ≥30% were observed in 7%, 50%, and 71% of patients. Median PFS was 5 months (range 1–11 months), median OS was 11 months (range 4–40 months). OS at 6, 12, 24, and 36 months was 74.2%, 44.5%, 14.8%, and 3.7%, respectively. Multivariable analysis showed no significant OS differences based on stratification. GEMDOC was tolerated, with 2 patients (7%) with grade 4 neutropenia and 1 (4%) with grade 3 febrile neutropenia. Common grade 1–3 adverse events were myelosuppression and fatigue. Treatment was discontinued in 36% due to adverse events, and 50% required growth factor support. Conclusions: Biweekly GEMDOC demonstrated activity in heavily pretreated mCRPC patients, showing notable PSA responses and survival benefits. Current literature reports that earlier approved therapies used after ADT and taxane-based regimens typically achieve OS and PFS of approximately 13 and 4 months. GEMDOC was well-tolerated, even in elderly patients, with manageable toxicity and minimal severe adverse events. These findings suggest the potential utility of this combination in addressing the needs of this challenging patient population. However, larger prospective studies are required to confirm its efficacy, optimize patient selection, and further evaluate safety profile. Patient baseline characteristics. Variable No. of Patients (%) Number of Prior Lines for mCRPC 1-2 7 (25) 3+ 21 (75) Prior Taxane Yes 26 (93) No 2 (7) ECOG PS 0 8 (29) 1 16 (57) ≥2 4 (14) Treatment Cycles Completed 2-4 13 (46) 5+ 15 (54)