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 - Funding Information:
Funding/Support and role of the sponsor: This investigator-sponsored trial received financial support from Sanofi and Janssen. The sponsors played a role in data collection.
Publisher Copyright:
© 2018 European Association of Urology
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. Overall survival among patients with metastatic castration-resistant prostate cancer treated with docetaxel, cabazitaxel, and a novel hormonal therapeutic agent is rather long. Docetaxel may lose some activity after an androgen receptor–targeted agent, while cabazitaxel seems to retain its activity whatever the treatment 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. Overall survival among patients with metastatic castration-resistant prostate cancer treated with docetaxel, cabazitaxel, and a novel hormonal therapeutic agent is rather long. Docetaxel may lose some activity after an androgen receptor–targeted agent, while cabazitaxel seems to retain its activity whatever the treatment sequence.
KW - Abiraterone
KW - Androgen receptor axis–targeted agents
KW - Cabazitaxel
KW - Castration-resistant prostate cancer
KW - Docetaxel
KW - Enzalutamide
KW - Sequence
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U2 - 10.1016/j.euo.2018.05.009
DO - 10.1016/j.euo.2018.05.009
M3 - Article
C2 - 31158090
AN - SCOPUS:85065645082
SN - 2588-9311
VL - 1
SP - 467
EP - 475
JO - European Urology Oncology
JF - European Urology Oncology
IS - 6
ER -