5063 Background: Recently, several new drugs have demonstrated an overall survival (OS) benefit in patients (pts) with mCRPC. Their use must be optimized to maximize patient outcomes. We evaluated prognostic factors of OS in mCRPC pts treated with cabazitaxel (C), a new taxane developed to overcome docetaxel (D) resistance. Methods: Records of 125 consecutive mCRPC pts (median 67 yrs) treated with C (after D) were retrospectively collected in 9 centers (France, n=8; Turkey, n=1). Baseline characteristics, disease history, PSA response, OS and radiological and/or clinical progression-free survival (PFS) were collected. The influence of selected variables on OS was analyzed by multivariate logistic regression. Results: At C initiation, 83.3% of pts were ECOG 0-1, 50.8% had an initial Gleason score of 8-10, 62.9% had pain and 84.8% had radiological or clinical progression. Median duration of response to first-line androgen deprivation therapy was 20 months (mo) and 22% received ≥2 prior D lines. New hormonal agents (abiraterone or enzalutamide) were given before C in 33% of pts and after C in 16%. Median number of C cycles received was 6 (range 2-14). A PSA decrease of ≥50% and ≥30% was reached in 41.3% and 48.8% of patients treated with C. Median OS from first C cycle was 13.3 mo and median clinical and/or radiological PFS was 6.5 mo. In multivariate analysis, OS was significantly reduced in pts with ECOG 2 (HR: 6.05), alkaline phosphatase ≥1.5 ULN (HR: 2.64), lymph node involvement (HR: 1.89). Conversely, OS was significantly prolonged in pts with ≥2 prior D lines (HR: 0.35), prior curative therapy (HR: 0.55), a PSA decrease ≥30% with C (HR: 0.21) and in pts treated with abiraterone/enzalutamide after C (HR: 0.37). Median OS from the first D dose was 65 mo in pts treated with abiraterone or enzalutamide after C versus 39 mo in pts receiving these agents before C. Conclusions: Patients with ≥ 2 prior D lines, PSA response ≥30% with C and treated with new hormonal agents after C experienced a prolonged OS. Conversely, intake of new hormonal agents before C rather than after was associated with a reduced OS from the first D dose. Prospective randomized trials are needed to confirm these results.