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]

Response to taxane chemotherapy as first subsequent therapy after abiraterone acetate (AA) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Post-hoc analysis of COU-AA-302.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 184-184 ◽  
Author(s):  
Johann Sebastian De Bono ◽  
Matthew Raymond Smith ◽  
Fred Saad ◽  
Dana E. Rathkopf ◽  
Peter F.A. Mulders ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Limited Information ◽  
Castration Resistant Prostate Cancer ◽  
Post Hoc Analysis ◽  
Kaplan Meier ◽  
Taxane Chemotherapy ◽  
Post Hoc

184 Background: In study COU-AA-302 of chemotherapy-naïve men with mCRPC, AA plus prednisone (AA) significantly improved radiographic progression-free survival and overall survival vs placebo plus prednisone (P). There is limited information about response to subsequent therapy after AA. In this post hoc analysis of pts in the AA treatment arm who progressed, we evaluated the clinical outcome to chemotherapy as first subsequent therapy. Methods: In COU-AA-302, 546 pts were randomized and received AA. Clinical outcome and discontinuation data from pts receiving chemotherapy as first subsequent therapy after progressing on AA were collected retrospectively and source verified. Median time to prostate-specific antigen (PSA) progression was estimated using the Kaplan-Meier method. Results: 73% (365/502; 44 still continuing on AA) of pts in the AA treatment arm received ≥ 1 subsequent therapy. Chemotherapy, docetaxel (DOC) or cabazitaxel (CBZ), was the most common first subsequent therapy. As of March 2014, following AA on study 53% (265/502) of pts received taxane chemotherapy (261 DOC, 4 CBZ) as first subsequent therapy. Median duration of first subsequent chemotherapy, mainly DOC, was 3 months (IQR, 1.0-5.0). Results are summarized (Table). Conclusions: This post hoc analysis describes antitumor activity in pts who progressed with AA and received taxane chemotherapy as first subsequent therapy. Despite the limitations of a retrospective analysis, these data support further assessment of subsequent therapies following AA treatment for mCRPC. Clinical trial information: NCT00887198. [Table: see text]

Treatment patterns after abiraterone acetate in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Post hoc analysis of COU-AA-302.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 168-168
Author(s):  
Thomas W. Flaig ◽  
Matthew R. Smith ◽  
Fred Saad ◽  
Dana E. Rathkopf ◽  
Peter F.A. Mulders ◽  
...  
Keyword(s):  
Study Drug ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Treatment Patterns ◽  
Limited Information ◽  
Castration Resistant Prostate Cancer ◽  
Post Hoc Analysis ◽  
Taxane Chemotherapy ◽  
Post Hoc ◽  
Baseline Psa

168 Background: Treatment patterns of mCRPC have changed substantially in the last few years. In COU-AA-302 (chemotherapy-naïve men with mCRPC), abiraterone acetate plus prednisone (AA) significantly improved radiographic progression-free survival and overall survival vs placebo plus prednisone (P). There is limited information about treatment patterns after AA. In this post hoc analysis of pts in the AA treatment arm who progressed, we characterized subsequent therapy after pts discontinued study drug. Methods: In COU-AA-302, 546 pts were randomized and received AA. Treatment patterns of pts receiving ≥ 1 subsequent therapy for mCRPC after progressing on AA were collected retrospectively and source verified. Results: As of March 2014, 8% (44/546) of pts continued on AA; 67% (365/546) received ≥ 1 subsequent therapy for mCRPC. 36% (194/546) and 15% (83/546) of pts had ≥ 2 and ≥ 3 subsequent therapies, respectively. 80% (435/543) of pts in the P arm had ≥ 1 subsequent therapy. Most frequent subsequent therapy in AA pts was taxane chemotherapy (docetaxel [DOC], cabazitaxel [CBZ]), androgen signaling–directed therapy (AA, enzalutamide [ENZ], ketoconazole [KETO]), and immunotherapy (sipuleucel-T [SIP-T]) (Table). Among AA pts who received DOC as first subsequent therapy, median age was 69 years; median duration of DOC post-AA (n = 261) was 3 months (IQR: 0.95-5.7); and PSA progression was the most common reason for discontinuation. Among AA pts with baseline PSA and ≥ 1 post-baseline PSA value, 40% (40/100) had ≥ 50% PSA decline (27/100 confirmed responses) with first subsequent DOC chemotherapy. Conclusions: This post hoc analysis indicates that treatment with subsequent therapy was common (67% and 80%) in pts with chemotherapy-naïve mCRPC who progressed with AA or P, respectively. PSA decline suggests antitumor activity in pts who progressed with AA and received subsequent DOC. Despite limitations of a retrospective analysis, these data support further assessment of subsequent therapy following AA treatment for mCRPC. Clinical trial information: NCT00887198. [Table: see text]

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.

Association of alkaline phosphatase (ALP) with clinical outcomes in chemotherapy-naive patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Results from COU-AA-302.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 27-27 ◽  
Author(s):  
Evan Y. Yu ◽  
Fred Saad ◽  
Anil Londhe ◽  
Neal D. Shore ◽  
Hendrik Van Poppel ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Cox Regression ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Prognostic Models ◽  
Castration Resistant Prostate Cancer ◽  
Increased Risk ◽  
Additive Risk ◽  
Post Hoc

27 Background: Prognostic models have been developed for men with mCRPC. In this analysis we undertook a pragmatic approach to focus on commonly obtained markers. Baseline ALP and normalization of elevated ALP post-docetaxel have prognostic value for overall survival (OS). We examined the association between ALP and prostate-specific antigen (PSA) elevation at baseline and after 4 cycles of therapy (C5D1), when both markers were assessed, with long-term clinical outcomes in COU-AA-302, a randomized phase 3 study of abiraterone acetate (AA) in chemotherapy-naive mCRPC pts. Methods: 1,088 pts were randomized 1:1 to AA (1 g) + prednisone (P) (5 mg BID) or placebo + P. Radiographic progression-free survival (rPFS) and OS were co-primary end points. The study design, as well as primary and secondary end point results obtained at the time of a prespecified interim analysis at 55% OS events, have been described in detail previously. The effect of elevated ALP (above upper limit of normal) and PSA (above 106.2 µg/mL, baseline third quartile) status on rPFS and OS was assessed retrospectively using a stratified Cox regression model that included treatment and baseline factors log (lactate dehydrogenase), hemoglobin, whether patient had only bone metastasis, and age. Results: Elevated status of ALP and PSA were independent significant predictors of increased risk for outcomes at baseline as well as after 4 cycles of therapy (Table). Conclusions: These post hoc analyses of data from COU-AA-302 suggest that elevated ALP and PSA at baseline and during treatment confers individual and additive risk for adverse clinical outcomes in chemotherapy-naive mCRPC. Clinical trial information: NCT00887198. [Table: see text]

scholarly journals Pain Progression at Initiation of Cabazitaxel in Metastatic Castration-Resistant Prostate Cancer (mCRPC): A Post Hoc Analysis of the PROSELICA Study

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1284
Author(s):  
Nicolas Delanoy ◽  
Debbie Robbrecht ◽  
Mario Eisenberger ◽  
Oliver Sartor ◽  
Ronald de Wit ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Radiological Progression ◽  
Post Hoc Analysis ◽  
Psa Response ◽  
Phase Iii Study ◽  
Psa Progression ◽  
Previously Treated ◽  
Post Hoc

Background: In the PROSELICA phase III trial (NCT01308580), cabazitaxel 20 mg/m2 (CABA20) was non-inferior to cabazitaxel 25 mg/m2 (CABA25) in mCRPC patients previously treated with docetaxel (DOC). The present post hoc analysis evaluates how the type of progression at randomization affected outcomes. Methods: Progression type at randomization was defined as follows: PSA progression only (PSA-p; no radiological progression (RADIO-p), no pain), RADIO-p (±PSA-p, no pain), or pain progression (PAIN-p, ±PSA-p, ±RADIO-p). Relationships between progression type and overall survival (OS), radiological progression-free survival (rPFS), and PSA response (confirmed PSA decrease ≥ 50%) were analyzed. Results: All randomized patients (n = 1200) had received prior DOC, and 25.7% had received prior abiraterone or enzalutamide. Progression type at randomization was evaluable in 1075 patients (PSA-p = 24.4%, RADIO-p = 20.8%, PAIN-p = 54.8%). Pain progression was associated with clinical and biological features of aggressive disease. Median OS from CABA initiation or date of mCRPC diagnosis, all arms combined, was shorter in the PAIN-p group than in the RADIO-p or the PSA-p groups (12.0 versus 16.8 and 18.4 months, respectively, p < 0.001). In multivariate analysis, all arms combined, PAIN-p was an independent predictor of poor OS (HR = 1.44, p < 0.001). PSA response, rPFS, and OS were numerically higher with CABA25 versus CABA20 in patients with PAIN-p. Conclusions: This post hoc analysis of the PROSELICA phase III study shows that pain progression at initiation of CABA in mCRPC patients previously treated with DOC is associated with a poor prognosis. Disease progression should be carefully monitored, even in the absence of PSA rise.

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]

Heterogeneous populations driven by clinical practice: A case example comparing enzalutamide (ENZA) and bicalutamide (BIC).

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. e571-e571
Author(s):  
Ruth Kim ◽  
M. Alan Brookhart ◽  
Scott Flanders ◽  
Neil M. Schultz ◽  
Jon Fryzek ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Baseline Period ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Heterogeneous Populations ◽  
Post Hoc Analysis ◽  
Insurance Claims Data ◽  
Comorbidity Index ◽  
Post Hoc ◽  
Cancer Network

e571 Background: Comparative real-world insurance claims data (RWD) analysis can be used to compare homogeneous cohorts (to avoid selection bias). Since the National Comprehensive Cancer Network guidelines recommend ENZA for metastatic castration-resistant prostate cancer (PC) and BIC for localized PC, it was of interest to evaluate these 2 heterogeneous cohorts as the ENZA cohort, being further advanced in the disease, has a worse prognosis than the BIC cohort. Here, we describe the results of a post hoc analysis on the ENZA and BIC cohorts to confirm the heterogeneity of demographics presented in a published study (Behl A et al. J Clin Oncol. 2016;34:235). Methods: The RWD captured enrollees with PC, claims for ENZA or BIC from 09/01/2012–12/31/2014, and at least 6 mo of continuous enrollment prior to the index date. After replicating methods from Behl et al using Truvan, we explored the balance of demographics in baseline periods greater than 6 mo. Differences in demographics and the post hoc analysis were compared. Results: Behl et al reported balanced age between the ENZA (73.1±10.0 y) and BIC (71.4±10.5 y) cohorts. However, 90% (531/592) of the ENZA cohort were metastatic vs 35% (1917/5524) of the BIC cohort. The Quan-Charlson comorbidity index was higher for the ENZA (5.6±2.1 y) than BIC (3.2±2.1 y) cohort. In the ENZA cohort, abiraterone acetate (ABI) or BIC utilization in the baseline period was higher (53%) than in the BIC cohort (0%). When the baseline period was greater than 6 mo, per our post hoc analysis, prior use of ABI or BIC increased to 68% for the ENZA cohort and remained unchanged in the BIC cohort. Conclusions: Despite results from the Behl analysis, the ENZA and BIC cohorts were dissimilar; ENZA patients had more advanced disease (metastatic disease; received ≥ 1 therapy) than BIC patients. Comparison of such heterogeneous populations can lead to biased estimates of treatment effects. Analyses lacking appropriate measures of prognostic variables that guide treatment decisions should be cautiously interpreted. Further analysis is required to identify best practices for using RWD and to address confounding driven by clinical practice.

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