159MO - Low-dose abiraterone with fatty food versus standard dose abiraterone in metastatic castration-resistant prostate cancer

Background

Standard dose of Abiraterone Acetate (AA) for metastatic CRPC is 1000mg/day in two divided doses to be taken on empty stomach. Food intake has shown alteration in pharmacokinetics of AA. Phase I studies have shown a 4.4 fold increase in drug absorption when taken with a high fat meal. Based on this hypothesis, studies have shown that low dose AA with a fatty meal is non inferior to standard dose. We did a prospective study of AA to confirm the same.

Methods

The primary objective of this study was to compare PSA response rate at 12 weeks with low dose (250mg) versus Standard dose (1000mg) Abiraterone Acetate. It was conducted from Dec 2019 to Dec 2020 and was a prospective randomised open-label study, where 70 consecutive patients with mCRPC were randomized in 1:1 ratio to receive low-dose AA ( 250 mg with a fatty meal) or Standard-dose AA (1000 mg in fasting state). Both groups received Prednisone at 5 mg twice daily. Recommended options for fatty meal included : a. Two teaspoons of Ghee b. Two teaspoons of Groundnut chutney c. Two teaspoons of clarified Butter.

Results

In the standard dose AA arm 32 out of 35 patients had bone metastasis while 3 patients had both bone and lymph nodal metastases. In low dose AA arm, 23 patients out of 35 had bone metastasis only while 12 patients had both bone and lymph nodal metastasis. Median baseline PSA level in the standard dose arm was 47 and in the low dose arm it was 65. At 12 weeks, in the standard AA arm, 2 patients out of 35 had PSA progression. The mean response to standard dose Abiraterone acetate was 68%. In the low dose AA arm, none of the patients had PSA progression. The mean response rate in the low dose arm was 82%. Fatigue (13 vs 12 patients in standard vs low dose arm respectively), Hypertension (12 vs 10 patients in standard vs low dose) hypokalaemia (11 patients in each arm) and fluid retention (9 vs 3 in standard vs low dose arm) were observed.

Conclusions

In metastatic CRPC, low dose AA taken with fatty meal is similar to standard dose AA in terms of PSA response and tolerance. In low resource countries like India, decreasing treatment costs will increase access to treatment, improve compliance and prevent interruption in treatment.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.