Sequencing of Taxanes and New Androgen-targeted Therapies in Metastatic Castration-resistant Prostate Cancer: Results of the International Multicentre Retrospective CATS Database

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.