Phase II study of abiraterone acetate in chemotherapy-naive metastatic castration-resistant prostate cancer displaying bone flare discordant with serologic response

Abstract

Purpose: Abiraterone is an oral inhibitor of CYP17, which is essential for androgen biosynthesis. This multicenter study assessed its efficacy in patients with castration-resistant prostate cancer (CRPC), without prior chemotherapy or CYP17-targeted therapy, and frequency of bone scans discordant with prostate-specific antigen (PSA) and clinical response.

Experimental design: Thirty-three patients received abiraterone acetate 1,000 mg daily with prednisone 5 mg twice daily in continuous 28-day cycles. Patients were evaluated monthly for efficacy and safety. Bone scan flare was defined as the combination, after 3 months of therapy, of an interpreting radiologist's report indicating "disease progression" in context of a 50% or more decline in PSA level, with scan improvement or stability 3 months later.

Results: A 50% or more decline in PSA level at week 12 was confirmed in 22 of 33 (67%) patients. Declines in PSA level of 50% or more were seen in 26 of 33 (79%) patients. Undetectable PSA levels (≤0.1 ng/mL) occurred in 2 patients. Median time on therapy and time to PSA progression were 63 weeks and 16.3 months, respectively. Twenty-three patients were evaluable for bone scan flare. Progression was indicated in radiologist's report in 12 of 23 (52%), and 11 of 12 subsequently showed improvement or stability. As prospectively defined, bone scan flare was observed in 11 of 23 (48%) evaluable patients or 11 of 33 (33%) enrolled patients. Adverse events were typically grade 1/2 and consistent with prior published abiraterone reports.

Conclusion: Clinical responses to abiraterone plus prednisone were frequent and durable in men with metastatic CRPC. Further investigation is needed to clarify the confounding effect of bone scan flare on patient management and interpretation of results. Clin Cancer Res; 17(14); 4854-61. ©2011 AACR.

Figure 1

Changes in prostate specific antigen (PSA) levels in castration-resistant prostate cancer (CRPC) patients treated with abiraterone acetate plus prednisone. Waterfall plots of maximal PSA change (top panel) and PSA change at week 12 (bottom panel).

Figure 2

Time to prostate specific antigen (PSA) progression in castration-resistant prostate cancer (CRPC) patients treated with abiraterone acetate and prednisone (n = 33). CI, confidence interval; NE=Not Estimable

Figure 3

Disposition of patients who did and did not experience a bone scan flare. *Of the 2 patients: 1 patient had a negative bone scan at baseline that was not repeated given the prostate specific antigen (PSA) decline; 1 patient came off study at month 4 due to a pathologic femoral neck fracture. ^†Of the 2 patients: 1 came off study after month 9 (and thus never underwent another bone scan) while the other patient came off study after month 16. BL= baseline; m4, month 4; m7, month 7

Figure 4

Examples of bone scan flare in patients receiving abiraterone acetate. (A) Example of a patient with a declining prostate specific antigen (PSA) but a month 4 bone scan being read as having a new metastasis in the right pubic ramus, as indicated by the arrow (although in retrospect one can see the lesion in the baseline bone scan). By month 7, this lesion shows improvement, indicating that this lesion seen at month 4 was present at baseline and thus was secondary to bone flare. (B) Example of a patient with a declining PSA but a month 4 bone scan being read as progression in existing lesions. By month 7, this progression has improved, indicating that the progression seen at month 4 was due to bone flare. BL= baseline,; m4, month 4; m7, month 7

Figure 4

Examples of bone scan flare in patients receiving abiraterone acetate. (A) Example of a patient with a declining prostate specific antigen (PSA) but a month 4 bone scan being read as having a new metastasis in the right pubic ramus, as indicated by the arrow (although in retrospect one can see the lesion in the baseline bone scan). By month 7, this lesion shows improvement, indicating that this lesion seen at month 4 was present at baseline and thus was secondary to bone flare. (B) Example of a patient with a declining PSA but a month 4 bone scan being read as progression in existing lesions. By month 7, this progression has improved, indicating that the progression seen at month 4 was due to bone flare. BL= baseline,; m4, month 4; m7, month 7