On Tuesday this week, three papers about abiraterone acetate were published in the on-line version of the Journal of Clinical Oncology. These articles are reports of data previously presented at various clinical/scientific meetings, but at least they are now available in a peer-reviewed journal.
In the first of the three papers, Reid et al. report on the antitumor activity of abiraterone in docetaxel-treated patients with castration-resistant prostate cancer (CRPC). This was a two-stage, Phase I/II study, and the first stage was met so we will only give the results of the full Phase II study. All patients were treated with 1,000 mg abiraterone acetate, once a day, and the study showed the following:
47 docetaxel-treated patients with CRPC were enrolled.
PSA declines of 30 percent or higher were observed in 32/47 patients (68 percent).
PSA declines of 50 percent or higher were observed in 24/47 patients (51 percent).
PSA declines of 90 percent or higher were observed in 7/47 patients (15 percent) of patients.
Partial responses (by RECIST criteria) were reported in 8/30 patients with measurable disease (27 percent).
The median time to PSA progression was 169 days.
The median number of weeks on study was 24.
12/47 patients (25.5 percent) remained on study for 48 weeks.
The levels of circulating T cells (CTCs) were assessed in 34 patients, of whom 27/34 (79 percent) had ≥ 5 CTCs at baseline; 11/27 patients (41 percent) had a decline from ≥ 5 to < 5 CTCs and 18/27 patients (67 percent) had a 30 percent decline in CTCs after starting treatment with abiraterone acetate.
In the second paper, Danila et al. report data from a trial designed to evaluate the efficacy and safety of abiraterone acetate in combination with prednisone to reduce the symptoms of secondary hyperaldosteronism that can occur with abiraterone monotherapy.
In this study, 58 men with progressive metastatic CRPC who experienced treatment failure with docetaxel-based chemotherapy received abiraterone (1,000mg once daily) with prednisone (5 mg twice daily). Nearly half of these patients (27/58 or 47 percent) had received prior ketoconazole.
The results of this study showed that:
A decline in PSA level of ≥ 50 percent or higher was confirmed in 22/58 patients (36 percent), including 14/31 patients (45 percent) who were ketoconazole-naïve and 7/27 patients (26 percent) who were ketoconazole-pretreated.
Partial responses were seen in 4/22 patients (18 percent) with RECIST-evaluable target lesions.
Improved ECOG performance scores were noted in 28 percent of patients.
The median time to PSA progression was 169 days.
CTC conversions with treatment from ≥ 5 to < 5 were noted in 10/29 patients (34 percent).
Taken together, the data from these two trials show that abiraterone + predisone had significant activity in heavily pretreated patients and that abiraterone alone has significant activity in docetaxel-treated patients with CRPC. The side effects associated with abiraterone acetate continue to be relatively minor, but the incidence of hypertension or hypokalemia in docetaxel-pretreated patients was reduced by adding low-dose prednisone to abiraterone acetate.
The third paper, by Ryan et al. provides additional information from a Phase I trial of abiraterone treatment in men who had all had ketoconazole therapy prior to treatment with abiraterone acetate.
On Tuesday this week, three papers about abiraterone acetate were published in the on-line version of the Journal of Clinical Oncology. These articles are reports of data previously presented at various clinical/scientific meetings, but at least they are now available in a peer-reviewed journal.
In the first of the three papers, Reid et al. report on the antitumor activity of abiraterone in docetaxel-treated patients with castration-resistant prostate cancer (CRPC). This was a two-stage, Phase I/II study, and the first stage was met so we will only give the results of the full Phase II study. All patients were treated with 1,000 mg abiraterone acetate, once a day, and the study showed the following:
In the second paper, Danila et al. report data from a trial designed to evaluate the efficacy and safety of abiraterone acetate in combination with prednisone to reduce the symptoms of secondary hyperaldosteronism that can occur with abiraterone monotherapy.
In this study, 58 men with progressive metastatic CRPC who experienced treatment failure with docetaxel-based chemotherapy received abiraterone (1,000 mg once daily) with prednisone (5 mg twice daily). Nearly half of these patients (27/58 or 47 percent) had received prior ketoconazole.
The results of this study showed that:
Taken together, the data from these two trials show that abiraterone + predisone had significant activity in heavily pretreated patients and that abiraterone alone has significant activity in docetaxel-treated patients with CRPC. The side effects associated with abiraterone acetate continue to be relatively minor, but the incidence of hypertension or hypokalemia in docetaxel-pretreated patients was reduced by adding low-dose prednisone to abiraterone acetate.
The third paper, by Ryan et al. provides additional information from a Phase I trial of abiraterone treatment in men who had all had ketoconazole therapy prior to treatment with abiraterone acetate.