Abiraterone acetate plus prednisone (AA+P) without continuing LHRH-therapy in patients with metastatic chemotherapy: Naive castrations-resistant prostate cancer—Results from the SPARE-trial (NCT02077634).

Abstract

5046 Background: The value of continuation of androgen deprivation therapy (ADT) in metastatic castration-resistant prostate cancer (CRPC) remains controversial and clear evidence is lacking. Especially upon treatment with the life-prolonging cytochrome P450 17-alpha-hydroxylase/C17,20 lyase (Cyp17)-inhibitor, abiraterone acetate (AA), which in combination with prednisone (P), has the ability to further suppress serum testosterone levels over ADT alone, continuation of ADT seems to be negligible. Methods: The exploratory phase II trial randomized CRPC patients to receive continued ADT plus AA+P versus AA+P alone (NCT02077634), funded by Jansen-Cilag GmbH, Germany. The primary endpoint was rate of rPFS at month 12, not powered for a direct comparison between treatment arms. Secondary endpoints included PSA response rate, objective response, time to PSA progression and safety. Results: Altogether, 67 patients were randomized between 08/2014 to 04/2017. Median testosterone-levels (T) remained far below castrate-levels throughout treatment in all patients. However, in 6 patients (18%) from Arm B, T-levels increased above castrate levels within 28 days after cessation of AA+P treatment. Median treatment duration is shorter in Arm A. Safety analysis is underway and results will be presented. Conclusions: Results of this exploratory study suggest that treatment with AA+P without ADT may be effective in patients with mCRPC and that ADT may not be necessary in patients receiving AA+P. In some patients, serum-testosterone levels may rise rapidly upon treatment discontinuation so that the levels should be monitored closely. Clinical trial information: NCT02077634. [Table: see text]

Testosterone recovery after androgen deprivation therapy in prostate cancer: building a predictive model

“…Our study could be relevant to decide when to nish the treatment with LHRH agonists if we want our patient to recover testosterone and improve his quality of life, but also when we desire to maintain castration avoiding the use and the side effects of these drugs, maybe even in progressive, mCRPC treated with other drugs, as abiraterone [23][24]. The SPARE trial, a multicenter, prospective, randomized, exploratory phase II study, and the retrospective, non-randomized study of Jha et al have evaluated the e cacy of abiraterone plus prednisone alone, without ADT, with excellent results compared to the three drugs together [2][3] and as in the pivotal study COU-AA-302 [25]. In this scenario, mCRPC, we can expect a long time of treatment with ADT before its withdrawal.…”

“…However, two recent studies question the need to maintain ADT in the setting of metastatic castration-resistant prostate cancer (mCRPC). The combination of abiraterone with prednisone without ADT could be comparable in terms of e cacy with standard treatment with all three drugs together [2][3].…”

Testosterone Recovery after Androgen Deprivation Therapy in Prostate Cancer: Building a Predictive Model

“…Our study could help clinicians decide when to conclude treatment with LHRH agonists not only if we want the patient to recover his testosterone level, thereby improving his quality of life, but also when we want the patient to maintain the castrate level while avoiding the side effects of the chemical castration drugs; this may also be feasible in patients with progressive mCRPC treated with other drugs, such as abiraterone [ 24 25 ]. The SPARE trial, a multicenter, prospective, randomized, exploratory phase II study, and the retrospective, nonrandomized study performed by Jha and Jeff [ 3 ] evaluated the efficacy of abiraterone plus prednisone alone, without ADT, and achieved excellent results compared to those of the three drugs together [ 2 3 ], as in the pivotal study COU-AA-302 [ 26 ]. In the case of mCRPC, we can expect a long duration of treatment with ADT before its cessation.…”

“…Two recent studies questioned the need to maintain ADT in metastatic castration-resistant PCa (mCRPC). The combination of abiraterone with prednisone without ADT could be comparable with standard treatment involving all three drugs [ 2 3 ].…”

A phase 2 randomized clinical trial of abiraterone plus ADT, apalutamide, or abiraterone and apalutamide in patients with advanced prostate cancer with non-castrate testosterone levels (LACOG 0415)

“…Interestingly, our study demonstrated for the first time that APA plus AAP might also promote a clinically significant decrease in testosterone levels, reaching castration levels in most patients. It has also been observed that abiraterone alone, a selective, irreversible inhibitor of CYP17, an enzyme that is critical in the production of androgens in the testes, adrenal glands, and prostate-tumour tissue, was associated with a significant, sustained decrease in testosterone levels due to suppression of the testosterone/androstenedione axis in humans [22,23]. Moreover, ongoing trials are evaluating neoadjuvant abiraterone in combination with apalutamide or enzalutamide in high-risk localized prostate cancer, and at the same time trials with an intensification of neoadjuvant ADT plus ASI have been reported [14,24e27].…”