Suppression of testosterone production using abiraterone acetate (AA) with or without androgen deprivation therapy (ADT) in metastatic castration resistant prostate cancer (mCRPC).

Abstract

5049 Background: Patients with metastatic prostate cancer (mPC) are treated with lifelong ADT even after progression and every treatment for mPC has been tested only in the setting of androgen deprivation. Androgen synthesis inhibitor AA which inhibits synthesis of androgen that later get converted to testosterone has been studied and approved only alongside ADT similar to all other agents that have no or limited activity on testosterone suppression. We reviewed the ability of AA to sufficiently suppress testosterone levels as compared to AA plus ADT and its potential impact on cost savings. Methods: This retrospective study included consecutive patients with mCRPC treated with AA alone or in combination with ADT (in absence of orchiectomy) who had been followed with serial testosterone values on therapy. A cost analysis was performed to determine the cost avoidance by omitting leuprolide injections while on AA. The cost avoidance was calculated by multiplying the total number of injections by the wholesale acquisition cost of $5252.86 for a three month leuprolide injection. Results: Of 57 patients included in the final analysis, 36 received AA plus ADT, 10 received AA alone, and 11 started off with AA plus ADT before transitioning to AA alone. Testosterone levels were drawn 235 times. Testosterone was undetectable (below < 2 ng/dl) in both arms, 134 of 152 in combination arm and 86 of 99 in the AA alone arm. The median testosterone concentration when detectable was 3 ng/dL in AA alone and 3.5 ng/dL in AA plus ADT. None in the combination arm and only one testosterone value in AA arm had testosterone > than 30 ng/dl. The mean duration of AA use in this study was close to one year, and the total duration of therapy was approximately 61 years which could result in elimination of 244 leuprolide administrations and approximately $1.29 million in total cost savings. Conclusions: AA alone is able to effectively suppress testosterone synthesis in patients with prostate cancer. ADT with GnRH agonist or antagonist can be safely withheld while on therapy with AA and testosterone values followed to confirm adequate androgen suppression. This has acquired new significance after studies in patients with hormone sensitive disease where median duration of treatment was 33 months which could translate to an avoidable expense of $55.5 million for 960 patients in ‘STAMPEDE’ study and $34.5 million in ‘LATITUDE’ study from leuprolide administration in combination arm.