RT Journal Article
T1 Cabazitaxel activity in men with metastatic castration-resistant prostate cancer with and without DNA damage repair defects
A1 Aldea, Mihaela
A1 Lam, Laurent
A1 Orillard, Emeline
A1 Llacer Perez, Casilda
A1 Saint-Ghislain, Mathilde
A1 Gravis, Gwenaelle
A1 Flechon, Aude
A1 Roubaud, Guilhem
A1 Barthelemy, Philippe
A1 Ricci, Francesco
A1 Priou, Frank
A1 Neviere, Zoe
A1 Beaufils, Mathilde
A1 Laguerre, Brigitte
A1 Hardy, Anne-Claire
A1 Helissey, Carole
A1 Ratta, Raffaele
A1 Borchiellini, Delphine
A1 Pobel, Cedric
A1 Joly, Florence
A1 Castro, Elena
A1 Thiery-Vuillemin, Antoine
A1 Baciarello, Giulia
A1 Fizazi, Karim
K1 DNA damage repair
K1 BRCA
K1 Cabazitaxel
K1 PARP inhibitors
K1 mCRPC
K1 Treatment outcomes
K1 Gene-mutations
K1 Phase-iii
AB Background: Cabazitaxel was shown to improve overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) after abiraterone/enzalutamine and docetaxel failure, though benefit by the presence of DNA damage repair (DDR) defects is unknown. With the advent of poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) in partially overlapping indications with cabazitaxel, we aimed to determine cabazitaxel activity in men with mCRPC according to their DDR status.Methods: This is a retrospective multicenter study that enrolled patients with mCRPC treated with cabazitaxel who had undergone DDR tumour tissue profiling. Patients with at least one deleterious germline or somatic alterations were considered DDR positive (DDR+). Each DDR + patient has been matched with a DDR negative (DDR-) from the same institution who underwent the same test. An exploratory cohort of patients found to be DDR + by liquid biopsy was also included. Prostate specific antigen (PSA) decline >= 50% (PSA50), PSA progression-free survival (PFS, PSA-PFS), radiographic PFS (rPFS), clinical PFS or radiographic PFS (c/rPFS) and OS were evaluated.Results: Among 190 men (95 DDR+, 95 DDR-) with tissue sequencing, PSA50 was achieved with cabazitaxel in 29/92 (32%) and 33/92 (36%) in patients with DDR+ and DDR(P = 0.64). The median rPFS was 5.33 months [9 5%CI 4.34-7.04] versus 5.75 months [95%CI 4.67-7.27] (P = 0.55). The median OS was 15.4 months [95%CI 12.16-26.6] and 11.5 months [95%CI 9.76-14.4] (P = 0.036), respectively. No PSA50 responses on cabazitaxel were observed in BRCA1/2 patients previously treated with PARPi (n = 10). Similar outcomes with cabazitaxel were observed in the liquid biopsy cohort (n = 63 DDR+).Conclusions: Our study suggests that cabazitaxel is active in patients with mCRPC regardless of their DDR status, although its activity in men pretreated with a PARPi may be lower. (C) 2021 Elsevier Ltd. All rights reserved.
PB Elsevier sci ltd
SN 0959-8049
YR 2021
FD 2021-11-02
LK https://hdl.handle.net/10668/26859
UL https://hdl.handle.net/10668/26859
LA en
DS RISalud
RD Apr 10, 2025