scholarly journals To switch or not to switch? A real-life experience using dexamethasone in combination with abiraterone

2019 ◽  
Vol 11 ◽  
pp. 175628721985490 ◽  
Author(s):  
Elisa Zanardi ◽  
Davide Soldato ◽  
Maria Maddalena Latocca ◽  
Carlo Cattrini ◽  
Francesco Boccardo
Keyword(s):  
Primary Endpoint ◽  
Life Experience ◽  
Specific Antigen ◽  
Real Life ◽  
Case Series ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Subsequent Treatment ◽  
Castration Resistant Prostate Cancer ◽  
Radiological Progression

The recently published phase II prospective SWITCH trial evaluated whether patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate could benefit from a ‘steroid switch’ from prednisone to dexamethasone. A total of 26 patients, both chemonaïve (14 patients) or pretreated with docetaxel (12 patients), with biochemical and/or limited radiological progression, were enrolled in this trial. Primary endpoint was prostate specific antigen (PSA) 30 defined as the proportion of patients with a PSA level decline 30% or more after 6 weeks of treatment with abiraterone acetate + dexamethasone. Secondary endpoints were: a PSA50 rate (defined as the proportion of patients with PSA decline of 50% or more after 12 weeks on abiraterone acetate + dexamethasone), biochemical and radiological progression-free survival (bPFS and rPFS, respectively), benefit from subsequent treatment and identification of biomarkers of response. Primary endpoint was reached in 46.2% of patients (12 patients), and two patients had an objective partial response on computed tomography scan. Median bPFS and rPFS were 5.3 months and 11.8 months. We present a case series of 11 patients who were consecutively treated with a steroid switch at our institution from January 2016 to August 2018 to investigate if this strategy could be used in a ‘real-life’ setting. We observed a PSA30 response in two patients (18%), median bPFS was 4.77 months (95% confidence interval [CI] 2.5–14.6) and median rPFS was 7.2 months (95% CI 3.8–15.5). Seven patients had a radiological stable disease as best response to steroid switch. Three patients were being still treated with abiraterone acetate + dexamethasone at data cut-off time. Our case series confirms that switching from prednisone to dexamethasone during abiraterone acetate treatment produces biochemical and radiological responses in both a predocetaxel and a postdocetaxel setting, providing a clinical benefit in mCRPC patients. However, to date, there is no clear indication as to which patient could benefit most from this kind of strategy.

Response to androgen signaling (AS)-directed therapy after treatment with abiraterone acetate (AA) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Post hoc analysis of study COU-AA-302.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 21-21 ◽  
Author(s):  
Matthew R. Smith ◽  
Shannon Matheny ◽  
Fred Saad ◽  
Dana E. Rathkopf ◽  
Peter F.A. Mulders ◽  
...  
Keyword(s):  
Clinical Response ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
Abiraterone Acetate ◽  
Subsequent Treatment ◽  
Limited Information ◽  
Castration Resistant Prostate Cancer ◽  
Post Hoc Analysis ◽  
Post Hoc

21 Background: In study COU-AA-302 of men with mCRPC and no prior chemotherapy, AA plus prednisone (hereafter AA) significantly increased radiographic progression-free survival. There is limited information about response to subsequent AS-directed therapies following AA. In this post hoc analysis of pts who received AA during study COU-AA-302, we evaluated clinical response to subsequent AA or enzalutamide (ENZ). Methods: In COU-AA-302, 546 pts were randomized and received AA. Subsequent response and discontinuation data from 88 pts receiving AS-directed therapy after study were collected retrospectively, source verified, and entered into the database. Median time to prostate-specific antigen (PSA) progression with 95% confidence intervals was estimated using the Kaplan-Meier method. Results: As of May 2013, following AA on study, 55 pts received subsequent AA and 33 received subsequent ENZ. 69% (38/55) of pts in the AA then AA group and 67% (22/33) pts in the AA then ENZ group received intervening chemotherapy. Baseline patient characteristics were similar across both groups and to the overall COU-AA-302 population. Median (range) exposure to subsequent therapy was 4 (1-20) months for AA and 5 (1-12) months for ENZ. Response to subsequent AA or ENZ is summarized in the Table. Conclusions: In this post hoc analysis, pts previously treated with AA experienced modest clinical response on subsequent treatment with either AA or ENZ. These data support further studies of subsequent AS-targeted drugs following treatment with AA for mCRPC. Clinical trial information: NCT00887198. [Table: see text]

TALAPRO-1: A phase II study of talazoparib (TALA) in men with DNA damage repair mutations (DDRmut) and metastatic castration-resistant prostate cancer (mCRPC)—First interim analysis (IA).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 119-119 ◽  
Author(s):  
Johann S. De Bono ◽  
Niven Mehra ◽  
Celestia S. Higano ◽  
Fred Saad ◽  
Consuelo Buttigliero ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Primary Endpoint ◽  
Radiographic Progression ◽  
Objective Response ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Circulating Tumor Cell ◽  
Abiraterone Acetate ◽  
Phase 2 ◽  
Castration Resistant Prostate Cancer

119 Background: Phase 2 and 3 studies with poly(ADP-ribose) polymerase inhibitors (PARPi) have demonstrated antitumor activity in patients (pts) with mCRPC with DDRmut who were previously treated with novel hormonal therapy (NHT). We report the first IA of a Phase 2 study of TALA, a potent inhibitor and trapper of PARP. Methods: TALAPRO-1 (NCT03148795) is enrolling pts (N ≈ 100) with measurable soft tissue disease, progressive mCRPC, and DDRmut likely to sensitize to PARPi (including ATM, ATR, BRCA1, BRCA2, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C), who received 1–2 chemotherapy regimens (≥1 taxane-based) and progressed on ≥1 NHT (enzalutamide/abiraterone acetate). Pts receive oral TALA 1 mg/d (moderate renal impairment, 0.75 mg/d) until radiographic progression, unacceptable toxicity, or consent withdrawal. Primary endpoint is objective response rate (ORR; blinded independent review). Secondary endpoints are time to OR, duration of response, prostate-specific antigen (PSA) decrease ≥50%, circulating tumor cell (CTC) count conversion (to CTC = 0 and <5 per 7.5 mL of blood), time to PSA progression, radiographic progression-free survival (rPFS), overall survival, safety, pt-reported outcomes, and pharmacokinetics. A planned IA of safety and efficacy was performed after 20 pts with BRCA1/2 mutations were on treatment for ≥8 wks. Results: 81 pts received TALA as of June 5, 2019; 43 pts enrolled by Feb 12, 2019 were evaluable for the primary endpoint (20 BRCA1/2, 2 PALB2, 14 ATM, 7 other). All had received docetaxel and 49% prior cabazitaxel. Overall ORR (95% CI) was 25.6% (13.5–41.2), ORRBRCA1/2 50.0% (27.2–72.8), ORRATM 7.1% (0.2–33.9). Overall median (95% CI) rPFS was 5.6 months (mo) (3.5–8.2), rPFSBRCA1/2 8.2 mo (5.6–NE), rPFSATM 3.5 mo (1.7–8.1). Most common treatment-emergent adverse events (≥20%) were anemia, nausea, asthenia, decreased appetite, constipation, and platelet count decreased. Conclusions: TALA monotherapy demonstrates encouraging antitumor activity in docetaxel-pretreated mCRPC pts, especially those with BRCA1/2mut, and was generally well tolerated. This study was sponsored by Pfizer Inc. Clinical trial information: NCT03148795.

scholarly journals Comparison of the oncological outcomes of abiraterone acetate and enzalutamide in metastatic castration-resistant prostate cancer: A multicenter real-life data

2021 ◽  
Author(s):  
Ayşe Demirci ◽  
Cemil Bilir ◽  
Burcu Gülbağcı ◽  
İlhan Hacibekiroğlu ◽  
İbrahim V.Bayoğlu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Factors ◽  
Specific Antigen ◽  
Real Life ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Factors Affecting ◽  
Castration Resistant ◽  
Number Of Patients

Abstract Background: To compare enzalutamide (E) and abiraterone acetate (AA) in terms of efficacy, survival and prognostic factors affecting survival in metastatic castration-resistant prostate cancer (mCRPC) patients. Methods: A total of 250 patients treated with E or AA in 5 centers were included.Results: The number of patients with no prostate specific antigen (PSA) decline was higher in the AA group than that in the E group, and the proportion of patients with a PSA decline of ≥50% was higher in the E group (p = 0.020). The rate of progression in the AA group (82.2%) was significantly higher than that in the E group (p <0.001). Radiological progression free survival (rPFS) and overall survival (OS) were significantly longer in the E group when compared to that in the AA group (p <0.001 and p = 0.027, respectively). In the E group, rPFS was significantly longer than that in the AA group in both pre- and post-docetaxel settings (p=0.010 and p=0.003, respectively). OS was similar in the pre-docetaxel setting; but in the post-docetaxel setting, E group had a significantly longer OS than the AA group(p=0.021). In the multivariate analysis performed in the whole patient group, we found that good prognostic factors for rPFS were E treatment, being ≥75 years and a PSA decline of ≥50% while there was no factor affecting OS. Conclusion: With longer OS and PFS, E seems to be more suitable for mCRPC patients in the post-docetaxel setting than AA.

scholarly journals Comparison of real-life data of abiraterone acetate and enzalutamide in metastatic castration-resistant prostate cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ayşe Demirci ◽  
Cemil Bilir ◽  
Burcu Gülbağcı ◽  
İlhan Hacıbekiroğlu ◽  
İbrahim V. Bayoğlu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Factors ◽  
Specific Antigen ◽  
Real Life ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Factors Affecting ◽  
Castration Resistant ◽  
Number Of Patients

AbstractTo compare enzalutamide (E) and abiraterone acetate (AA) in terms of efficacy, survival and to characterize prognostic factors affecting survival in metastatic castration-resistant prostate cancer (mCRPC) patients. A total of 250 patients treated with E or AA in 5 centers were included. The number of patients with no prostate specific antigen (PSA) decline was higher in the AA group than that in the E group, and the proportion of patients with a PSA decline of ≥ 50% was higher in the E group (p = 0.020). Radiological progression free survival (rPFS) and overall survival (OS) were significantly longer in the E group when compared to that in the AA group (p < 0.001 and p = 0.027, respectively). In the E group, rPFS was significantly longer than that in the AA group in both pre- and post-docetaxel settings (p = 0.010 and p = 0.003, respectively). OS was similar in the pre-docetaxel setting; but in the post-docetaxel setting, E group had a significantly longer OS than the AA group (p = 0.021). In the multivariate analysis performed in the whole patient group, we found that good prognostic factors for rPFS were E treatment, being ≥ 75 years and a PSA decline of ≥ 50% while there was no factor affecting OS. With longer OS and PFS, E seems to be more suitable for mCRPC patients in the post-docetaxel setting than AA.

scholarly journals Prognostic factors for patients treated with abiraterone

2020 ◽  
Vol 6 (2) ◽  
pp. FSO436 ◽  
Author(s):  
Cecília M Alvim ◽  
André Mansinho ◽  
Rita S Paiva ◽  
Raquel Brás ◽  
Patrícia M Semedo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Hazard Ratio ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Prognostic And Predictive Factors

Aim: To evaluate prostate-specific antigen response (PSAr) defined as a ≥50% decrease in PSA concentration from the pretreatment value, as a prognostic factor in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA). Methods: Retrospective evaluation of patients with mCRPC treated with AA. Results: 124 patients were identified. Median overall survival and progression-free survival for patients achieving PSAr versus patients without PSAr were 29.3 versus 9.7 months and 17.0 versus 5.2 months, respectively. Multivariate analysis confirmed that PSAr correlated with better overall survival (hazard ratio: 0.19; 95% CI: 0.10−0.38; p < 0.001) and progression-free survival (hazard ratio: 0.24; 95% CI: 0.14−0.41; p < 0.001). Conclusion: PSAr can be utilized as prognostic and predictive factors in mCRPC patients treated with AA.

Does Gleason score (GS) predict efficacy of abiraterone acetate (AA) therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC)? An analysis of AA phase 3 trials.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 20-20 ◽  
Author(s):  
Karim Fizazi ◽  
Thomas W. Flaig ◽  
Carsten-Henning Ohlmann ◽  
Howard I. Scher ◽  
Johann Sebastian De Bono ◽  
...  
Keyword(s):  
Clin Oncol ◽  
Cox Model ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Initial Diagnosis ◽  
Castration Resistant Prostate Cancer ◽  
Treatment Benefit ◽  
Kaplan Meier ◽  
The Impact

20 Background: GS is strongly prognostic in localized PC but is less so in mCRPC (Halabi S, J Clin Oncol 2003; Armstrong AJ, Eur J Cancer 2010). Pts with high-risk localized PC and high GS who undergo radiation therapy benefit from long-term androgen deprivation therapy (Horwitz EM, J Clin Oncol 2008). In mCRPC, the impact of GS at initial diagnosis on response to AA therapy is unknown. We retrospectively evaluated efficacy outcomes in pts with mCRPC treated with AA plus prednisone (P) vs P alone in pivotal studies COU-AA-301 (post-docetaxel) and COU-AA-302 (chemo-naive) by GS (≥ 8 or < 8). Methods: 1,048 pts in COU-AA-301 and 996 in COU-AA-302 with mCRPC treated with AA 1 g + P 5 mg po BID or placebo + P had GS data at diagnosis. Efficacy end points evaluated: overall survival (OS), radiographic progression free survival (rPFS), and time to prostate-specific antigen progression (TTPP) (de Bono JS, NEJM 2011; Fizazi K, Lancet Oncol 2012; Ryan CR, NEJM 2013). Distributions and medians were estimated by the Kaplan-Meier method, and hazard ratio (HR) and 95% confidence interval were estimated by the Cox model. Results: Proportion of pts with GS ≥ 8 and GS < 8 was similar across treatment groups and studies. Outcomes by GS are summarized in the Table. Conclusions: GS (≥ 8 or < 8) at initial diagnosis was not predictive of treatment benefit of AA + P vs P alone in post-docetaxel and chemo-naïve pts with mCRPC, with both groups benefiting. In this era of novel androgen signaling targeted agents, GS may not be relevant in predicting efficacy with AA for pts with mCRPC. Clinical trial information: NCT00638690, NCT00887198. [Table: see text]

Real-world treatment with abiraterone acetate in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC).

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 239-239 ◽  
Author(s):  
Martin Boegemann ◽  
Martin Hatzinger ◽  
Dirko Hercher ◽  
Geoffrey Matus ◽  
Els Grieta Everaert ◽  
...  
Keyword(s):  
Real World ◽  
Treatment Duration ◽  
Radiographic Progression ◽  
Real Life ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Rank Test ◽  
Castration Resistant Prostate Cancer ◽  
Similar Treatment

239 Background: In the COU-AA-302 trial, abiraterone acetate plus prednisone (AAP) resulted in extension of radiographic progression-free survival (rPFS) and overall survival in chemotherapy-naïve mCRPC patients compared to prednisone alone. However, limited data on AAP treatment and outcomes is available in the real-world in this setting. The aim of this study is to describe the duration of AAP treatment in routine clinical practice in mCRPC patients prior to chemotherapy. Methods: The study was designed as a retrospective chart review of mCRPC patients identified through oncology and urology practice in Belgium, France, Germany and the UK. This first analysis reports baseline patient characteristics at AAP initiation for the first 224 patients. Treatment duration, PFS and rPFS were estimated using Kaplan-Meier curves. Potential factors associated with treatment duration were explored using the log-rank test. Results: Data from 224 mCRPC patients treated with AAP (Belgium: 67; Germany: 150; UK: 7; none from France) across 19 centres was considered in this initial analysis. At baseline, the median age was 75.5 years (interquartile range [IQR]: 69.0-82.0) and the median PSA level was 50.0 ng/mL (IQR: 21.0-121.0). Patients with visceral metastases (9.8%) and ECOG 2-3 (9.4%) were included in this study, in contrast to those included in the COU-AA-302 study. Median duration of AAP treatment was 11.6 months (95% confidence interval [CI]: 10.2-12.8), whilst median PFS and rPFS were 11.9 months (95% CI: 10.8-13.3) and 16.5 months (95% CI: 13.5-20.0), respectively. Reasons for discontinuing AAP involved PSA progression (52.2%), radiographic progression (38.9%), symptomatic progression (27.8%), non-toxic death (19.4%) and toxicity (2.2%). Treatment duration was significantly longer in mCRPC patients with either baseline ECOG status 0, lower PSA, alkaline phosphatase, aspartate aminotransferase, or lactate dehydrogenase levels (p < 0.05). Conclusions: The results of this study suggest similar treatment duration and rPFS for mCRPC patients in this real-life cohort with poorer clinical features compared to those observed in the COU-AA-302 trial population.

Concomitant intake of abiraterone and food to increase pharmacokinetic exposure: Real-life data from a therapeutic drug monitoring program.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3117-3117 ◽  
Author(s):  
Stefanie L. Groenland ◽  
Andre M. Bergman ◽  
Alwin Huitema ◽  
Neeltje Steeghs
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Monitoring Program ◽  
Real Life ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Fixed Dose ◽  
Therapeutic Drug ◽  
Castration Resistant Prostate Cancer ◽  
Regular Treatment

3117 Background: Abiraterone acetate is registered for the treatment of metastatic castration resistant prostate cancer. Pharmacokinetic (PK) exposure has been linked to efficacy, since patients with Cmin ≥ 8.4 ng/mL have a significantly longer progression free survival compared to patients with a Cmin below this threshold (7.4 vs. 12.2 months, p = 0.044) (Carton, 2017). At the recommended fixed dose of 1000 mg QD administered in a modified fasting state, 35% of patients do not reach this efficacy threshold (Carton, 2017), providing a strong rationale for therapeutic drug monitoring (TDM). Since a clinically relevant food effect has been established, concomitant intake of abiraterone and food could offer a cost-neutral solution in case of low exposure (Chi, 2015). This study aims to evaluate whether PK-guided abiraterone dosing is feasible and results in an increased proportion of patients with concentrations above the target. Methods: Patients starting regular treatment with abiraterone were included. PK sampling occurred 4, 8 and 12 weeks after start of treatment, and every 12 weeks thereafter. Abiraterone concentrations were measured and Cmin was calculated. In case of Cmin < 8.4 ng/mL and acceptable toxicity, a PK-guided intervention was advised. As a first step, concomitant intake of abiraterone and a light meal or a snack was advised. Results: In total, 35 patients were included, of which 18 patients (51%) had at least one Cmin < 8.4 ng/mL. These patients were advised to take abiraterone concomitantly with food, after which Cmin increased significantly from 5.6 (47%) ng/mL [mean (CV%)] to 40.6 (110%) ng/mL (p = 0.006) without additional toxicities. This intervention led to adequate exposure in 15 patients (83%). Seventeen patients had all Cmin levels ≥ 8.4 ng/mL, in these patients mean Cmin was 31.5 (65%) ng/mL. Conclusions: TDM of abiraterone was applied in clinical practice and proved to be feasible. Concomitant intake with food resulted into a significant increase in Cmin and offers a cost-neutral opportunity to optimize treatment for patients with low PK exposure. Up to 100 patients will be included to evaluate the effect of PK-guided abiraterone dosing on treatment efficacy. Clinical trial information: NL6695.

scholarly journals Efficacy and safety of abiraterone acetate plus prednisolone in patients with early metastatic castration-resistant prostate cancer who failed first-line androgen-deprivation therapy: a single-arm, phase 4 study

2020 ◽  
Author(s):  
K Kobayashi ◽  
N Okuno ◽  
G Arai ◽  
H Nakatsu ◽  
A Maniwa ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Androgen Deprivation Therapy ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Androgen Deprivation ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Castration Resistant

Abstract Aim The aim was to evaluate the efficacy and safety of abiraterone acetate plus prednisolone in patients with chemotherapy-naïve early metastatic castration-resistant prostate cancer who failed first-line androgen deprivation therapy. Methods Patients with early metastatic castration-resistant prostate cancer with confirmed prostate-specific antigen progression within 1-year or prostate-specific antigen progression without having normal prostate-specific antigen level (&lt;4.0 ng/mL) during first-line androgen deprivation therapy were enrolled and administered abiraterone acetate (1000 mg) plus prednisolone (10 mg). A minimum of 48 patients were required according to Simon’s minimax design. The primary endpoint was prostate-specific antigen response rate (≥50% prostate-specific antigen decline by 12 weeks), secondary endpoints included prostate-specific antigen progression-free survival and overall survival. Safety parameters were also assessed. Results For efficacy, 49/50 patients were evaluable. Median age was 73 (range: 55–86) years. The median duration of initial androgen deprivation therapy was 32.4 (range: 13.4–84.1) weeks and 48 patients experienced prostate-specific antigen progression within 1-year after initiation of androgen deprivation therapy. prostate-specific antigen response rate was 55.1% (95% confidence interval: 40.2%–69.3%), median prostate-specific antigen–progression-free survival was 24.1 weeks, and median overall survival was 102.9 weeks (95% confidence interval: 64.86 not estimable [NE]). Most common adverse event was nasopharyngitis (15/50 patients, 30.0%). The most common ≥grade 3 adverse event was alanine aminotransferase increased (6/50 patients, 12.0%). Conclusions Abiraterone acetate plus prednisolone demonstrated a high prostate-specific antigen response rate of 55.1%, suggesting tumor growth still depends on androgen synthesis in patients with early metastatic castration-resistant prostate cancer. However, prostate-specific antigen–progression-free survival was shorter than that reported in previous studies. Considering the benefit–risk profile, abiraterone acetate plus prednisolone would be a beneficial treatment option for patients with chemotherapy-naive metastatic prostate cancer who show early castration resistance.

SPARTAN, a phase 3 double-blind, randomized study of apalutamide (APA) versus placebo (PBO) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 161-161 ◽  
Author(s):  
Eric Jay Small ◽  
Fred Saad ◽  
Simon Chowdhury ◽  
Boris A. Hadaschik ◽  
Julie Nicole Graff ◽  
...  
Keyword(s):  
Distant Metastasis ◽  
Randomized Study ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Distant Metastases ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
End Points ◽  
Free Survival

161 Background: Pts with nmCRPC are at risk for developing metastatic disease and cancer-specific mortality. There are no approved treatments for nmCRPC. APA is an orally administered next-generation androgen receptor inhibitor with antitumor activity in CRPC. SPARTAN evaluated the effects of APA on metastasis-free survival (MFS) in men with nmCRPC. Methods: Pts with nmCRPC and prostate-specific antigen doubling time (PSADT) of ≤ 10 mos were randomized 2:1 to APA (240 mg QD) or PBO. The primary end point was MFS, defined as the time from randomization to first radiographic distant metastasis (per blinded central review) or death. Secondary end points included time to metastasis (TTM), progression-free survival (PFS), time to symptomatic progression (SymProg), and overall survival (OS). Pts were eligible to receive study-provided abiraterone acetate plus prednisone after developing distant metastases. Second progression-free survival (PFS2, the time from randomization to disease progression or death after first treatment for metastatic CRPC) was also evaluated. Results: 1207 pts were randomized. Baseline PSADT was < 5 mos in both groups. APA decreased the risk of distant metastasis or death by 72% (HR = 0.28; 95% CI, 0.23-0.35; p < 0.0001), with a median MFS of 40.5 vs 16.2 mos in the PBO group. Secondary end points (TTM, PFS, and SymProg) were all significantly improved. At an interim analysis for OS, there was a trend favoring APA. At a median follow-up of 20.3 mos, 61% of APA and 30% of PBO pts were still on treatment. Rates of discontinuation due to adverse events were low in both groups (10.7% APA, 6.3% PBO). Mean baseline health-related quality of life scores were maintained with treatment, with no difference between groups over time. Of those whose disease progressed, 80% of PBO and 56% of APA pts received therapy for metastatic CRPC. PFS2 was significantly longer for APA vs PBO. Conclusions: APA significantly improved median MFS by 2 years in men with nmCRPC. APA also significantly increased TTM, PFS, SymProg, and PFS2. APA was associated with improved OS. These results support the addition of APA to androgen deprivation therapy in men with nmCRPC. Clinical trial information: NCT01946204.

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