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Background Although the benefit of androgen deprivation therapy (ADT) continuation in metastatic castration-resistant prostate cancer (mCRPC) remains controversial, clinical evidence is lacking. Recent results indicated that treatment with abiraterone acetate (AA) plus prednisone (P) further suppresses serum testosterone levels over ADT alone, suggesting that continuation of ADT in the treatment of mCRPC may not be necessary. Methods In this exploratory phase 2 study, mCRPC patients were randomized with a 1:1 ratio to receive either continued ADT plus AA + P (Arm A) or AA + P alone (Arm B). The primary endpoint was the rate of radiographic progression-free survival (rPFS) at month 12. Secondary endpoints included PSA-response rate, objective response, time to PSA progression and safety. Results A total of 68 patients were equally randomized between the two study arms. Median testosterone-levels remained below castrate-levels throughout treatment in all patients. According to the intention-to-treat analysis the rPFS rate was 0.84 in Arm A and 0.89 in Arm B. Moderate and severe treatment-emergent adverse events were reported for 72% of the patients in Arm A and for 85% of the patients in Arm B. Conclusions AA + P treatment without ADT may be effective in mCRPC patients and ADT may not be necessary in patients receiving AA + P.

BackgroundThe value of continuation of luteinizing hormone-releasing hormone (LHRH) therapy in castration-resistant prostate cancer (CRPC) remains controversial and clear evidence is lacking. Argumentation for cessation of LHRH therapy is the prolonged suppression of testosterone levels after the withdrawal of LHRH analogues and the fact that disease progression occurs despite castration levels of testosterone. Especially upon treatment with the life-prolonging cytochrome P450 17-alpha-hydroxylase (Cyp17)-inhibitor, abiraterone, which has the ability to further suppress testosterone serum levels over LHRH therapy alone, continuation of LHRH therapy seems to be negligible. However, the proven increase of luteinizing hormone levels after LHRH withdrawal, which is even further increased by abiraterone, may counteract the effects of abiraterone by the induction of enzymes of steroidogenesis. Therefore, cessation of LHRH therapy when starting treatment with abiraterone in CRPC may display an unpredictable hazard to the patients. This study will explore the role of continuation of LHRH therapy when starting treatment with abiraterone in patients with asymptomatic or mildly symptomatic, chemotherapy-naïve CPRC.Methods/designThe trial will assess radiographic progression-free survival after 12 months of treatment with abiraterone/prednisone in patients who will be randomized to receive continuing LHRH therapy versus LHRH withdrawal at the time of starting abiraterone therapy.DiscussionThis multicenter, prospective, randomized, exploratory phase-II trial will bring about new data regarding the efficacy and safety of abiraterone/prednisone treatment with or without continuation of LHRH therapy. In addition, further insight into the complex hormonal changes under treatment will be gained and the results of this trial may give rise to a larger phase-III trial to examine the possibility of withdrawing LHRH therapy in patients with CRPC.Trial registrationClinicalTrials.gov, ID: NCT02077634. Registered on 9 December 2013.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-2195-x) contains supplementary material, which is available to authorized users.

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]

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