Original Study
Results of the FLAC European Database of Metastatic Castration-Resistant Prostate Cancer Patients Treated With Docetaxel, Cabazitaxel, and Androgen Receptor–Targeted Agents

https://doi.org/10.1016/j.clgc.2018.02.016Get rights and content

Abstract

Background

Several agents have demonstrated an overall survival (OS) benefit in patients with metastatic castration-resistant prostate cancer (mCRPC); however, the optimal sequencing of these therapies is unknown as a result of a lack of prospective randomized controlled trials. This retrospective study aimed to identify clinical factors influencing outcomes and to determine optimal treatment sequencing in patients with mCRPC treated with cabazitaxel (CABA) and/or androgen receptor–targeted agents (ART) after androgen-deprivation therapy (ADT) and docetaxel (DOC).

Patients and Methods

Records of 574 consecutive patients treated (2012−2016) at 44 centers in 6 countries were retrospectively examined.

Results

A total of 267 patients received ADT → DOC → CABA (group 1), 183 patients ADT → DOC → ART → CABA (group 2), and 124 patients ADT → DOC → CABA → ART (group 3), with respective median OS from diagnosis of mCRPC of 38.3, 44.45, and 53.9 months (P = .012 for group 3 vs. group 1). Multivariate analysis showed response to first ADT ≤ 12 months, Gleason score of 8 to 10, clinical progression, and high prostate-specific antigen levels at mCRPC diagnosis were associated with worse OS. Prior receipt of ART did not influence activity of CABA.

Conclusion

OS appeared to increase with the number of life-extending therapies, with a sequence including DOC, CABA, and an ART providing the greatest OS benefit.

Introduction

Management of metastatic castration-resistant prostate cancer (mCRPC) has dramatically evolved within the past few years, with 6 agents having demonstrated an overall survival (OS) benefit: docetaxel (DOC), cabazitaxel (CABA), sipuleucel T (United States only), next-generation androgen receptor–targeted agents (ART) such as abiraterone acetate or enzalutamide, and radium-223.1 CABA has demonstrated an OS benefit similar to DOC in chemonaive mCRPC patients who did not receive an ART.2 Conversely, it prolongs OS in patients with progressive disease with or after DOC.3 It also retains activity in patients whose disease is progressing with receipt of ART.4

The challenge is to integrate this broad armamentarium rationally into daily practice and appropriately tailor therapies to optimize patient outcomes. However, the optimal sequencing of CABA with these other life-extending therapies is unknown because prospective randomized controlled trials are lacking.5, 6 Therefore, this noninterventional, observational study examined OS with various treatment sequences and sought to identify factors influencing OS in a real-life international cohort of mCRPC patients treated with CABA.

Section snippets

Patient Selection and Data Collection

Data were retrospectively collected (using an electronic case report form) from consecutive mCRPC patients (as per European Association of Urology definition1) treated between August 2012 and July 2016 at 44 centers in France, Spain, the United Kingdom, Greece, Poland, and Turkey. Patients were selected for inclusion in the study if they had received CABA for disease progression during or after DOC, with CABA administered as recommended—that is, at a dose of 25 mg/m2 (or exceptionally 20 mg/m2

Population Characteristics and Outcomes of Initiation of CABA

Overall, 574 mCRPC patients were treated with CABA in the participating centers according to 3 different sequences: group 1 (ADT → DOC → CABA), 267 patients; group 2 (ADT → DOC → ART → CABA), 183 patients; and group 3 (ADT → DOC → CABA → ART), 124 patients. Four patients received radium-223 as last therapy (1 patient in each of groups 1 and 2, and 2 patients in group 3); however, numbers were too small to perform any specific analysis.

Overall, 46.4% of patients had metastatic disease at

Discussion

To our knowledge, this is the largest cohort of mCRPC patients treated with CABA in real-life practice published to date. It documents outcomes of patients with mCRPC treated according to 3 different sequences of life-extending therapies: ADT → DOC → CABA only (historical arm because next-generation ART was not yet available at that time), ADT → DOC → CABA → ART, and ADT → DOC → ART → CABA. Results suggest that patients receiving 3 life-extending therapies (DOC, CABA, and ART, either

Conclusion

Our results suggest that OS of mCRPC patients increases with the number of life-extending therapies, with the greatest benefit being observed with a sequence including DOC, CABA, and ART. Limitations of a retrospective cohort apply. Randomized prospective trials are needed to confirm these data.

Disclosure

A.A. has received honoraria from Sanofi. S.O. has received consulting fees, travel support, and honoraria from Sanofi, Astellas, Bayer, and Janssen, and has served on advisory boards and lectured for Astellas, Sanofi, and Janssen. J.B. has received consulting fees, travel support, and honoraria from Sanofi, Astellas, and Janssen, and has served on advisory boards and lectured for Astellas, Sanofi, and Janssen. The other authors have stated that they have no conflict of interest.

Acknowledgments

English-language editing was provided by Andrea Bothwell. Supported in part by Association pour la Recherche sur les Thérapeutiques Innovantes en Cancérologie (ARTIC) and by Sanofi and Janssen, France.

References (31)

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