[Early- vs. late-onset treatment using abiraterone acetate plus prednisone in chemo-naïve, asymptomatic or mildly symptomatic patients with metastatic CRPC after androgen deprivation therapy].

BACKGROUND

Abiraterone acetate (AA) is a prodrug of abiraterone, which is an irreversible inhibitor of 17α-hydroxylase/C17, 20-lyase. Since 2011, abiraterone acetate has been available in combination with prednisone/prednisolone (AA + P) for the treatment of metastatic castration-resistant prostate cancer (mCRPC) after pre-treatment with docetaxel, and since 2012 for the treatment of chemotherapy-naïve asymptomatic or mildly symptomatic mCRPC patients. A revision of the guidelines of the European Association of Urology in 2014 redefining castration resistance gave rise to the question of when the treatment of mCRPC with abiraterone acetate plus prednisone should be initiated after prior hormone treatment and how successful it would be. This led us to observe an early-onset AA + P therapy cohort (EC) and a late-onset therapy cohort (LC) of patients.

PATIENTS AND METHODS

We designed a combined retrospective and prospective, multicentre, non-interventional two-cohort study to obtain data on the effectiveness and safety of an early-onset AA + P therapy in mCRPC patients in the clinical routine compared to a late therapy onset. The EC comprised patients who received AA + P immediately after castration resistance without a prior first-generation antiandrogen such as bicalutamide or flutamide. The LC included patients who, after castration resistance had occurred, started treatment with AA + P only after unsuccessful treatment with a first-generation antiandrogen. Patients with mCRPC who received AA + P therapy according to the physician's routine clinical practice decision were considered. The patients were consecutively included in the study on the basis of their medical records, with the treatment decision having been made independently of and before patient enrolment. Patients were documented or followed from the beginning of AA + P therapy until the start of a carcinoma-specific systemic follow-up therapy (retrospectively if before and prospectively if after start of data collection). Effectiveness analyses were done for all patients with at least two AA + P administrations and safety analyses for all treated patients.

RESULTS

Of the 159 patients included, 44 received early therapy and 105 received later therapy with AA + P. 10 patients could not be clearly assigned and were summarised in a third cohort (missed early-onset therapy assignment; MEC). 56/159 patients (35.2 %) were still alive at study start and 103/159 patients (64.8 %) had already deceased (31/44 [70.5 %] in EC, 64/105 [61.0 %] in LC, and 8/10 [80.0 %] in MEC). 24/159 patients (15.1 %) were documented both retrospectively and prospectively. The median duration of AA + P treatment was 11.3 months for EC, 12.0 months for LC, and 8.3 months for MEC patients. The median time to next systemic cancer therapy or death was 12.3 months for EC and 12.8 months for LC patients (p = 0.2820). The median time to the next systemic cancer therapy alone (i. e. without the event 'death') was 22.7 months for EC and 23.3 months for LC patients (p = 0.5995). Median overall survival (OS) was 22.3 months for EC and 39.2 months for LC patients (p = 0.0232). The incidence of serious adverse events (SAEs) was low. SAEs occurred in 3/44 EC (6.8 %), 4/105 LC (3.8 %), and 1/10 MEC patients (10.0 %). One SAE in EC and one in LC resulted in death.

CONCLUSIONS

In contrast to the new definition of castration resistance, AA + P was still more frequently used in daily clinical practice during the study observation period in patients treated with antiandrogens of the first generation after occurrence of castration resistance. Nevertheless, AA + P therapy appears to be effective and well tolerated during clinical routine in mCRPC patients. A comparison of the study results with earlier 'real-world' studies, however, has to take limiting factors into account. The observed difference in median overall survival might be explained by the imbalance of baseline characteristics between both cohorts with regard to number of patients, patients already deceased at start of documentation, patients with visceral metastases and patients with opioids at start of AA + P. For these reasons, patients in the EC initially might have had a poorer prognosis. A prospective randomised and controlled clinical trial would therefore be necessary to assess a possible difference in overall survival and response of the AA + P treatment with respect to therapy onset.