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

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 Cab→Abi (cabazitaxel prior to abiraterone) and Abi→Cab before July 10th, 2013, respectively. Median OS was 19.1 months and 17.0 months in Cab→Abi and Abi→Cab treated patients, respectively (p = 0.369). Median PFS and biochemical PFS were significantly longer in Cab→Abi 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, Abi→Cab treated patients had a significantly decreased antitumor response from cabazitaxel than Cab→Abi 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.

Role of chemotherapy in the treatment of metastatic castration-resistant prostate cancer patients who have progressed after abiraterone acetate

“…Specifically, despite the limitations of non-randomized retrospective studies, the CAST [17] report was the first to investigate the outcomes of C followed by abiraterone acetate and vice versa in two groups of patients following progression while on D. In this study, the activity of C as a third-line therapy was found to be inferior compared with its use as a second-line therapy in the other group. It is likely that the presence of constitutively activated androgen receptor splice variants, which generally lack the carboxy-terminal ligand-binding domain, resulted in resistance to abiraterone acetate and enzalutamide but were still inhibited by tubulin-binding drugs [15].…”

“…The activity of C following abiraterone acetate has been investigated in five studies [15][16][17][18][19]. Specifically, despite the limitations of non-randomized retrospective studies, the CAST [17] report was the first to investigate the outcomes of C followed by abiraterone acetate and vice versa in two groups of patients following progression while on D. In this study, the activity of C as a third-line therapy was found to be inferior compared with its use as a second-line therapy in the other group.…”

“…In 2014, Wissing and colleagues [17] retrospectively examined the clinical outcomes and safety profiles of (subgroups of) Dutch metastatic CRPC patients who had been treated with both C and abiraterone acetate after receiving D as first-line therapy (CAST study). The efficacy of C was investigated in 69 patients.…”

“…Cabazitaxel has been evaluated in patients who have previously been treated with both D and abiraterone acetate in five retrospective studies [15][16][17][18][19].…”

Oncologic Response and Hospitalization Rate of Patients Receiving Cabazitaxel in the Fourth-Line and Beyond in Castration-Resistant Prostate Cancer: Analysis of a Retrospective Cohort and a Structured Literature Review

“…This could be a rationale for CAB treatment in the fourth-line. There is limited literature data with a small series of patients on current treatment with CAB beyond third-line therapies for CRPC, as shown in Table 3 [7,[16][17][18][19][20][21][22]. In third-or fourth-line CAB, the median PFS is reported around 4 months and most of the patients died within a year.…”