Phase II trial of abiraterone acetate (AA) treatment for metastatic prostate cancer (PC) patients with a PSA of more than four following initial androgen deprivation therapy: SWOG S1014.
152 Background: Metastatic PC patients with a poor response to initial androgen deprivation therapy (ADT) as reflected by a PSA &gt; 4 ng/ml after 7 months of ADT have a poor prognosis. In the S9346 trial, about 25% of all enrolled patients had a PSA &gt; 4 ng/ml after 7 months of ADT with a subsequent median survival (OS) of 13 months. S1014 examined the efficacy of AA in this setting. Methods: Eligible patients with metastatic PC and a PSA of &gt; 4ng/ml between 6-12 months after starting ADT were treated with 1,000 mg of AA daily + 5 mg of prednisone twice daily. PSA could be rising or falling at the time of enrollment, but had to be &gt; 4 ng/ml. No chemotherapy or secondary hormonal therapies were allowed, except in patients receiving an anti-androgen at the time of enrollment, who were continued on this therapy. The primary endpoint was a PSA of ≤ 0.2ng/ml within 12 months of starting AA. The null hypothesis was a 5% rate and alternative was 20%, requiring 6 or more patients with PSA &lt; 0.2 ng/ml to conclude the regimen is promising (one-sided α=0.048, power=0.92). Results: Forty-one patients were enrolled between 7/2012 and 7/2013. One patient was deemed not analyzable due to not receiving any protocol treatment. Fourteen patients remain on treatment. Five (13%) patients achieved an undetectable PSA of ≤ 0.2ng/ml (95% CI 4%, 27%). Nine (23%) additional patients had PSA level &gt; 0.2 but &lt; 4 ng/ml. Twenty-one patients had no PSA response and six were not assessable and assumed to be non-responders. The median progression-free survival (PFS) was 17.4 months. There was one incident each of Grade 4 ALT elevation and rectal bleeding. Twelve patients reported Grade 3 adverse events as their worst level of severity. Conclusions: Although encouraged by 5 patients attaining “undetectable” PSA responses to AA in this poor prognosis setting, this study did not reach the protocol pre-specified level of 6 responses. OS and PFS will be updated with further follow-up. The therapy was generally well tolerated, without any clear signal of any unexpected toxicity. Clinical trial information: NCT01309672.