Real-world outcome with abiraterone low-dose plus prednisone in patients with mCRPC in a Brazilian Public Cancer Center.

Abstract

e17563 Background: Abiraterone acetate (AA) is a potent selective and irreversible inhibitor of CYP17 used as standard treatment for metastatic Castration Resistant Prostate Cancer (mCRPC). In the pivotal trial COU-AA 301, AA 1000 mg/day plus prednisone increased overall survival after docetaxel in patients with mCRPC. A recent trial demonstrated not inferiority with respect to PSA metrics in the reduced dose of 250mg/day AA associated with dietary intake, which is described as AA low dose (AALD). The introduction of generic AA in the Brazilian Pharma Market and after the endorsement of AALD from international guidelines, the use of AA in limited resourced hospitals became feasible. Since december 2018 our institution has incorporated AALD in patients with mCRPC in first or second line therapy, always after chemotherapy with Docetaxel (either in the sensitive or castration scenario). Methods: We retrospectively reviewed 49 patients with mCRPC that received AALD after chemotherapy with Docetaxel from December 2018 to January 2019. The primary end point was PSA response rate (decrease of ≥ 50% in the PSA concentration from pretreatment PSA value). Univariable analysis were performed to explore association between clinical and pathological features. Results: After a median follow-up of 5 months, 25 patients (51%) had PSA response rate ≥ 50%. Median age was 69 years-old and most patients (73.5%) were ECOG 0 and 1. Despite good ECOG, the population had aggressive disease characteristics with 57.1% being ISUP 4 and 5 and 69.4% being clinical stage IV at initial diagnosis. Seventeen patients (34.7%) were exposed to AALD at first line and 32 patients (65.3%) in second line. It was observed that patients in the first line had better PSA response rate them those treated in the second line (70,6% vs 40,6%. p 0.04). Conclusions: Despite the premature data, this retrospective analyses shows PSA response rate in about 50% of patients treated with AALD in the overall population and about 70% in those treated in first line therapy. Serum PSA response rate is known as a surrogate marker for overall survival in those patients. The protocol will for more mature data. AALD might be an alternative dose for treating patients in institutions with limited resources.

The Right Dose: From Phase I to Clinical Practice

“…68 The development of this dosing regimen is particularly surprising given the lack of dose-response and marked food effects evident in Cougar's phase I study. 139 More recently, a randomized study demonstrated the apparent equivalence of 250 mg with food (low-fat breakfast) and the labeled dosing regimen, 33 leading to incorporation of this off-label dosing regimen in National Comprehensive Cancer Network guidelines, 140 soon followed by adoption in India, 141 Brazil, 142 and Thailand. 143 Furthermore, given the prolonged effect of a single dose of this irreversible inhibitor, it is likely that a 500-mg dose administered with food every 2 to 7 days may be as effective as the labeled dosing regimen of 1,000 mg once daily on an empty stomach.…”