CAST: A retrospective analysis of cabazitaxel and abiraterone acetate sequential treatment in patients with metastatic castrate-resistant prostate cancer previously treated with docetaxel

MD Wissing, JLLM Coenen, Paul van den Berg, HM Westgeest, AJM (Fons) van den Eertwegh, IM van Oort, MM Bos, AM Bergman, P Hamberg, AJ Tije, M Los, Martijn Lolkema, Ronald de Wit, H Gelderblom

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Abstract

Cabazitaxel and abiraterone have both received approval for treating metastatic castrate-resistant prostate cancer (mCRPC) patients after first-line docetaxel therapy. In the cabazitaxel and abiraterone sequential treatment (CAST) study, the clinical outcome of docetaxel-treated mCRPC patients treated sequentially with both cabazitaxel and abiraterone was studied. Data were collected retrospectively from mCRPC patients at 12 hospitals across the Netherlands who initiated cabazitaxel and/or abiraterone before December 2012. Primary outcome measure was overall survival (OS); secondary measures were progression-free survival (PFS), biochemical PFS, and best clinical and PSA response. Hospital admission data during treatment were collected, as well as toxicities resulting in treatment discontinuation or patient death. Sixty-three and 69 patients received CabAbi (cabazitaxel prior to abiraterone) and AbiCab before July 10th, 2013, respectively. Median OS was 19.1 months and 17.0 months in CabAbi and AbiCab treated patients, respectively (p = 0.369). Median PFS and biochemical PFS were significantly longer in CabAbi treated patients: 8.1 versus 6.5 (p = 0.050) and 9.5 versus 7.7 months (p = 0.024), respectively. Although partial responses to cabazitaxel occurred in both groups, AbiCab treated patients had a significantly decreased antitumor response from cabazitaxel than CabAbi treated patients (median PFS 5.0 versus 2.6 months, p < 0.001). Minor differences in toxicities were observed based on therapy sequence; generally, toxicity from cabazitaxel could be severe, while abiraterone toxicity was milder. This retrospective analysis indicates that primary progression on cabazitaxel or abiraterone did not preclude a response to the other agent in mCRPC patients. However, tumor response of both agents, particularly cabazitaxel, was lower when administered as higher-line therapy in the selected study population. What's new? Novel agents have been introduced to treat patients with metastatic castrate-resistant prostate cancer (mCRPC). Among those are cabazitaxel, a second-generation taxane, and abiraterone, which inhibits testosterone biosynthesis through blockade of cytochrome p450 c17. This retrospective study evaluated clinical outcome of cabazitaxel and abiraterone sequential treatment in docetaxel-treated mCRPC patients. Patient survival did not differ significantly based on treatment sequence. The antitumor efficacy of cabazitaxel was lower after abiraterone, but prior treatment with one agent did not preclude a response to the other. Toxicity of the two drugs differed, with cabazitaxel having greater potential for severe toxicity.
Original languageUndefined/Unknown
Pages (from-to)E760-E772
JournalInternational Journal of Cancer
Volume136
Issue number6
DOIs
Publication statusPublished - 2015

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