TY - JOUR
T1 - Sequencing of Taxanes and New Androgen-targeted Therapies in Metastatic Castration-resistant Prostate Cancer
T2 - Results of the International Multicentre Retrospective CATS Database
AU - Delanoy, Nicolas
AU - Hardy-Bessard, Anne-Claire
AU - Efstathiou, Eleni
AU - Le Moulec, Sylvestre
AU - Basso, Umberto
AU - Birtle, Alison
AU - Thomson, Alastair
AU - Krainer, Michael
AU - Guillot, Aline
AU - De Giorgi, Ugo
AU - Hasbini, Ali
AU - Daugaard, Gedske
AU - Bahl, Amit
AU - Chowdhury, Simon
AU - Caffo, Orazio
AU - Beuzeboc, Philippe
AU - Spaeth, Dominique
AU - Eymard, Jean-Christophe
AU - Fléchon, Aude
AU - Alexandre, Jérôme
AU - Helissey, Carole
AU - Butt, Mohamed
AU - Priou, Frank
AU - Lechevallier, Éric
AU - Deville, Jean-Laurent
AU - Goupil, Marine Gross
AU - Morales, Rafael
AU - Thiery-Vuillemin, Antoine
AU - Gavrikova, Tatiana
AU - Barthelemy, Philippe
AU - Sella, Avishay
AU - Fizazi, Karim
AU - Baciarello, Giulia
AU - Fererro, Jean-Marc
AU - Laguerre, Brigitte
AU - Verret, Benjamin
AU - Hans, Sophie
AU - Oudard, Stéphane
N1 - Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.
PY - 2018/12
Y1 - 2018/12
N2 - BACKGROUND: The optimal sequence of life-extending therapies in metastatic castration-resistant prostate cancer (mCRPC) is unknown.OBJECTIVE: To evaluate outcomes among mCRPC patients treated with docetaxel (DOC), cabazitaxel (CABA), and a novel androgen receptor-targeted agent (ART; abiraterone acetate or enzalutamide) according to three different sequences.DESIGN, SETTING, AND PARTICIPANTS: Data from 669 consecutive mCRPC patients were retrospectively collected between November 2012 and October 2016.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the prostate-specific antigen (PSA) response (decrease ≥50% from baseline) to each therapy. Secondary endpoints included best clinical benefit, time to PSA progression, radiological progression-free survival (rPFS), overall survival (OS), and toxicity.RESULTS AND LIMITATIONS: A total of 158 patients received DOC→CABA→ART (group 1), 456 received DOC→ART→CABA (group 2), and 55 received ART→DOC→CABA (group 3). At baseline, PSA progression only and Gleason <8 were more common in group 3. PSA response on DOC was lower in group 3 than in other groups (p=0.02) and PSA response on CABA was higher in the second than in the third line (p=0.001). In Group 3, rPFS on ART (6.6 mo) and DOC (9.2 mo) was also shorter than in the other groups. OS calculated from the first life-extending therapy reached 34.8, 35.8, and 28.9 mo in groups 1, 2 and 3, respectively (p=0.007). Toxicity was comparable between the arms. The main limitations of the trial are its retrospective design and the low number of patients in group 3.CONCLUSIONS: In this retrospective trial, sequencing of DOC, CABA, and one ART, was associated with median OS of up to 35.8 mo. CABA seemed to retain its activity regardless of treatment sequence. DOC activity after ART appeared to be reduced, but the data are insufficient to conclude that cross-resistance occurs.PATIENT SUMMARY: The order of drugs administered to patients with metastatic castration-resistant prostate cancer could impact their efficacy, with cabazitaxel appearing to retain its activity whatever the therapeutic sequence.
AB - BACKGROUND: The optimal sequence of life-extending therapies in metastatic castration-resistant prostate cancer (mCRPC) is unknown.OBJECTIVE: To evaluate outcomes among mCRPC patients treated with docetaxel (DOC), cabazitaxel (CABA), and a novel androgen receptor-targeted agent (ART; abiraterone acetate or enzalutamide) according to three different sequences.DESIGN, SETTING, AND PARTICIPANTS: Data from 669 consecutive mCRPC patients were retrospectively collected between November 2012 and October 2016.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the prostate-specific antigen (PSA) response (decrease ≥50% from baseline) to each therapy. Secondary endpoints included best clinical benefit, time to PSA progression, radiological progression-free survival (rPFS), overall survival (OS), and toxicity.RESULTS AND LIMITATIONS: A total of 158 patients received DOC→CABA→ART (group 1), 456 received DOC→ART→CABA (group 2), and 55 received ART→DOC→CABA (group 3). At baseline, PSA progression only and Gleason <8 were more common in group 3. PSA response on DOC was lower in group 3 than in other groups (p=0.02) and PSA response on CABA was higher in the second than in the third line (p=0.001). In Group 3, rPFS on ART (6.6 mo) and DOC (9.2 mo) was also shorter than in the other groups. OS calculated from the first life-extending therapy reached 34.8, 35.8, and 28.9 mo in groups 1, 2 and 3, respectively (p=0.007). Toxicity was comparable between the arms. The main limitations of the trial are its retrospective design and the low number of patients in group 3.CONCLUSIONS: In this retrospective trial, sequencing of DOC, CABA, and one ART, was associated with median OS of up to 35.8 mo. CABA seemed to retain its activity regardless of treatment sequence. DOC activity after ART appeared to be reduced, but the data are insufficient to conclude that cross-resistance occurs.PATIENT SUMMARY: The order of drugs administered to patients with metastatic castration-resistant prostate cancer could impact their efficacy, with cabazitaxel appearing to retain its activity whatever the therapeutic sequence.
KW - Abiraterone Acetate/administration & dosage
KW - Aged
KW - Antineoplastic Combined Chemotherapy Protocols/administration & dosage
KW - Disease-Free Survival
KW - Docetaxel/administration & dosage
KW - Humans
KW - Male
KW - Middle Aged
KW - Multivariate Analysis
KW - Prostate-Specific Antigen/analysis
KW - Prostatic Neoplasms, Castration-Resistant/drug therapy
KW - Retrospective Studies
KW - Taxoids/administration & dosage
KW - Treatment Outcome
U2 - 10.1016/j.euo.2018.05.009
DO - 10.1016/j.euo.2018.05.009
M3 - Journal article
C2 - 31158090
SN - 2588-9311
VL - 1
SP - 467
EP - 475
JO - European urology oncology
JF - European urology oncology
IS - 6
ER -