Outcomes of initial vs delayed docetaxel therapy in veterans with metastatic hormone sensitive prostate cancer and high volume of disease.

Abstract

5097 Background: Docetaxel (DOC) continues to demonstrate efficacy in metastatic hormone sensitive prostate cancer (mHSPC), particularly in combination with androgen deprivation therapy (ADT) ± androgen receptor pathway inhibitors (ARPI). However, a paucity of data exists evaluating treatment sequencing with DOC for patients with high volume disease. We assessed overall survival (OS) of patients with mHSPC treated with either DOC followed by ARPIs or ARPIs followed by DOC. Methods: A nationwide retrospective study of 696 US Veterans with de novo (synchronous) mHSPC who received both DOC and an ARPI in combination with ADT in the Veterans Health Administration between 2015-2023. Of these, 581 (83.5%) had high-volume disease. Patients either received DOC (1) within 4 months of and (2) greater than 4 months after ADT. The early DOC group received an ARPI after the initial 4 months while the late DOC group received an ARPI within 4 months of ADT. Age, baseline PSA, Charlson comorbidity index (CCI) and BMI values were acquired for each patient. Survival analysis was performed using the Kaplan-Meier method. Results: Of the 581 Veterans with high-volume disease, 400 received DOC early (68.8%) and 181 received DOC later (31.2%). Patients who received DOC early had a significantly longer OS than those who received it later (median 36.3 vs 29.3 months, p<0.001, HR 0.65, 95% CI 0.53-0.80). Findings were similar when adjusted for age, baseline PSA, and CCI (aHR 0.69, 95% CI 0.56-0.85). Additionally, patients who received DOC early had a significantly longer rwPFS than those who received it later (median 17.0 vs 12.5 months, p<0.001, HR 0.63, 95% CI 0.52-0.76). Findings were similar when adjusted for age, baseline PSA, and CCI (aHR 0.64, 95% CI 0.53-0.78). Evaluation of baseline characteristics between DOC vs ARPI combination therapy showed that the early DOC group was younger (mean 66.4 vs 69.6 years, p<0.001). However, no other statistically significant differences were found between the two groups when comparing baseline PSA, BMI, and CCI. Conclusions: Initial DOC in Veterans with de novo high volume mHSPC was associated with longer survival. While all patients were candidates for chemotherapy, the Veterans who were treated early with DOC were younger. These finding support early docetaxel in patients with aggressive disease that are likely to develop castration-resistance and require subsequent therapies. Patient characteristics. Docetaxel Early (n=400) Docetaxel Late (n=181) p-value Age (mean) 66.4 69.6 < 0.001 Baseline PSA (median) 174 217 0.23 Creatinine Value (median) 1.00 1.02 0.1 BMI (mean) 28.7 28.0 0.06 Charlson Comorbidity Index (mean) 1.66 1.90 0.36