Final survival results from SPARTAN, a phase III study of apalutamide (APA) versus placebo (PBO) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5516-5516 ◽  
Author(s):  
Eric Jay Small ◽  
Fred Saad ◽  
Simon Chowdhury ◽  
Stephane Oudard ◽  
Boris A. Hadaschik ◽  
...  
Keyword(s):  
Cox Model ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Testing Procedure ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Free Survival ◽  
End Point ◽  
Final Survival

5516 Background: SPARTAN evaluated APA vs PBO in pts with nmCRPC and a prostate-specific antigen doubling time of ≤ 10 mo receiving androgen deprivation therapy (ADT). At primary end point analysis of metastasis-free survival (MFS), APA significantly improved median MFS by 2 yrs, as well as time to metastasis, progression-free survival, and time to symptomatic progression vs PBO (Smith, et al. NEJM 2018); overall survival (OS) results were immature. SPARTAN was unblinded upon meeting the primary end point; pts still on PBO were allowed to cross over to APA. Final survival results are reported herein. Methods: 1207 nmCRPC pts were randomized 2:1 to APA (240 mg QD) or PBO plus ongoing ADT. At progression, pts could receive open-label sponsor-provided abiraterone acetate + prednisone. After the primary efficacy end point (MFS) was met, 76 PBO pts (19%) crossed over to APA. OS and time to cytotoxic chemotherapy (TTCx) were tested by group sequential testing procedure with O’Brien-Fleming (OBF)-type alpha spending function. Time-to-event end points were analyzed by Kaplan-Meier method and Cox model. A sensitivity analysis for OS, accounting for crossover using a naïve censoring approach, was conducted. Results: With follow-up of 52.0 mo, 428 (of 427 required) OS events had occurred. Median treatment duration: APA, 32.9 mo; PBO, 11.5 mo. Median OS was significantly longer with APA + ADT vs PBO + ADT (73.9 vs 59.9 mo), (hazard ratio [HR], 0.784, Table). APA significantly lengthened TTCx (HR, 0.629). Discontinuation rates (APA vs PBO) due to progressive disease were 42.7% vs 73.9%, and due to adverse events (AE) 15.2% vs 8.4%. Safety was consistent with previous reports; grade 3/4 treatment-emergent (TE) AEs of special interest were rash 5.2%, fractures 4.9%, falls 2.7%, ischemic heart disease 2.6%, hypothyroidism 0%, and seizures 0%. 1 TEAE leading to death (myocardial infarction) was considered potentially APA related. Conclusions: In pts with nmCRPC, APA + ADT significantly improved OS compared with PBO + ADT, with median OS > 6 yr in the APA + ADT group and 14 mo improvement over PBO + ADT. Benefit from APA was observed despite a 19% crossover from PBO. The safety profile of APA was consistent with prior interim analyses. Clinical trial information: NCT01946204 . [Table: see text]

The occurrence of grade 4 adverse events and survival outcomes in patients with nonsquamous non-small cell lung cancer receiving bevacizumab with chemotherapy in the phase III PointBreak and AVAiL studies.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19022-e19022
Author(s):  
Liza Cosca Villaruz ◽  
Mark A. Socinski ◽  
Jyoti D. Patel ◽  
Larry Leon ◽  
Sebastien Hazard ◽  
...  
Keyword(s):  
Cox Model ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Free Survival ◽  
End Point ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Post Hoc ◽  
Unacceptable Toxicity ◽  
Clinical Trial Information

e19022 Background: Progression-free survival (PFS) is a key trial end point for clinical practice, as it relates to a change of treatment line. Grade 4 progression-free survival (G4PFS; defined as time from treatment start to the earlier of progressive disease [PD], onset of a G4 adverse event [AE], or death from any cause) is a composite end point incorporating a measure of tolerability to PFS. This post hoc analysis evaluates G4PFS and the effect of G4 AEs on PFS and overall survival (OS) in patients (pts) enrolled in PointBreak (PB) and AVAiL. Methods: Pts in PB were randomized to bevacizumab (BEV) 15 mg/kg q3w with carboplatin and paclitaxel (CP) or pemetrexed (CPem) for ≤4 cycles. Eligible pts received either BEV or BEV + Pem q3w until PD or unacceptable toxicity. Pts in AVAiL received cisplatin and gemcitabine for ≤6 cycles and either placebo or BEV (7.5 or 15 mg/kg) q3w until PD. AEs were graded via NCI-CTCAE v3.0. Kaplan-Meier and Cox model methods were used to estimate medians and hazard ratios (HRs) for PFS, G4PFS, and OS. PFS and OS were also compared in each arm for pts with occurrence of a G4 AE before week 12 of treatment vs those without. Results: Of those receiving BEV, ~30% of AVAiL pts and 38% of PB pts had a G4 AE. Uncomplicated neutropenia was the most common G4 AE in the CP + BEV arm of PB (26%) and in the BEV arms of AVAiL (11%). PFS, G4PFS, and outcomes by G4 AE occurrence are shown (Table). Conclusions: In both the PB and AVAiL trials, median G4PFS was numerically shorter than median PFS. G4 AE occurrence, however, did not affect subsequent PFS or OS in either trial. Clinical trial information: NCT00762034 and NCT00806923. [Table: see text]

Updated analysis of progression-free survival with first subsequent therapy (PFS2) and safety in the SPARTAN study of apalutamide (APA) in patients (pts) with high-risk nonmetastatic castration-resistant prostate cancer (nmCRPC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 144-144 ◽  
Author(s):  
Eric Jay Small ◽  
Fred Saad ◽  
Simon Chowdhury ◽  
Stephane Oudard ◽  
Boris A. Hadaschik ◽  
...  
Keyword(s):  
High Risk ◽  
Distant Metastasis ◽  
Treatment Duration ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Significant Benefit ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Free Survival

144 Background: In the phase 3 SPARTAN study, compared with placebo (PBO), APA, a next-generation androgen receptor inhibitor, decreased the risk of distant metastasis or death by 72% (hazard ratio [HR], 0.28; p < 0.0001) in men with high-risk nmCRPC. After 1 year of additional follow-up, PFS2 and safety were reevaluated to ensure maintenance of benefit against potential harm. Methods: Pts with nmCRPC and prostate-specific antigen doubling time of ≤ 10 mos were randomized 2:1 to APA (240 mg QD) + androgen deprivation therapy (ADT) or PBO + ADT. All pts who developed distant metastasis, determined by blinded independent central review, were eligible to receive subsequent therapy including open-label treatment with abiraterone acetate + prednisone, provided by the sponsor. The exploratory PFS2 end point (time from randomization to disease progression on subsequent anticancer therapy or death) was evaluated, as was incidence of treatment-emergent adverse events (TEAEs). Results: Median treatment duration with APA was 25.7 mos; with PBO, 11.5 mos (original analysis, mos: APA, 19.2; PBO, 11.2). Pts randomized to APA continued to show significant benefit in PFS2 (HR, 0.5; 95% CI, 0.39-0.63; p < 0.0001) vs PBO (APA median time to PFS2 not reached vs PBO 39.3 mos). At a median follow-up of 32 mos, 51.3% of pts receiving APA, 8% of the 75 pts who crossed over from PBO to APA, and 99.7% of remaining PBO pts had discontinued study treatment. Rates of discontinuations due to progressive disease and AEs were 27.3% and 12.7%, respectively, in the APA group and 73.4% and 8.4% in the PBO group. There was no substantial change in the incidence of TEAEs in the APA group at the 1-year update. With regard to drug specific TEAEs, there were no grade 4 or 5 events; grade 3 TEAEs consisted of rash, 5.2%; falls, 2.4%; fractures, 3.1%; hypothyroidism, 0%; and seizures, 0%. Conclusions: APA was previously shown to result in an improvement in metastasis-free survival and symptomatic progression. With a median APA treatment duration of 25.7 mos, APA continues to show significant benefit in PFS2, and its safety profile remains unchanged. Clinical trial information: NCT01946204.

Randomized, Double-Blind, Phase III Trial of Ipilimumab Versus Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy-Naive Castration-Resistant Prostate Cancer

2017 ◽  
Vol 35 (1) ◽  
pp. 40-47 ◽  
Author(s):  
Tomasz M. Beer ◽  
Eugene D. Kwon ◽  
Charles G. Drake ◽  
Karim Fizazi ◽  
Christopher Logothetis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Castration Resistant ◽  
Grade 3

Purpose Ipilimumab increases antitumor T-cell responses by binding to cytotoxic T-lymphocyte antigen 4. We evaluated treatment with ipilimumab in asymptomatic or minimally symptomatic patients with chemotherapy-naive metastatic castration-resistant prostate cancer without visceral metastases. Patients and Methods In this multicenter, double-blind, phase III trial, patients were randomly assigned (2:1) to ipilimumab 10 mg/kg or placebo every 3 weeks for up to four doses. Ipilimumab 10 mg/kg or placebo maintenance therapy was administered to nonprogressing patients every 3 months. The primary end point was overall survival (OS). Results Four hundred patients were randomly assigned to ipilimumab and 202 to placebo; 399 were treated with ipilimumab and 199 with placebo. Median OS was 28.7 months (95% CI, 24.5 to 32.5 months) in the ipilimumab arm versus 29.7 months (95% CI, 26.1 to 34.2 months) in the placebo arm (hazard ratio, 1.11; 95.87% CI, 0.88 to 1.39; P = .3667). Median progression-free survival was 5.6 months in the ipilimumab arm versus 3.8 with placebo arm (hazard ratio, 0.67; 95.87% CI, 0.55 to 0.81). Exploratory analyses showed a higher prostate-specific antigen response rate with ipilimumab (23%) than with placebo (8%). Diarrhea (15%) was the only grade 3 to 4 treatment-related adverse event (AE) reported in ≥ 10% of ipilimumab-treated patients. Nine (2%) deaths occurred in the ipilimumab arm due to treatment-related AEs; no deaths occurred in the placebo arm. Immune-related grade 3 to 4 AEs occurred in 31% and 2% of patients, respectively. Conclusion Ipilimumab did not improve OS in patients with metastatic castration-resistant prostate cancer. The observed increases in progression-free survival and prostate-specific antigen response rates suggest antitumor activity in a patient subset.

scholarly journals ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide or Placebo in Men With Metastatic Hormone-Sensitive Prostate Cancer

2019 ◽  
Vol 37 (32) ◽  
pp. 2974-2986 ◽  
Author(s):  
Andrew J. Armstrong ◽  
Russell Z. Szmulewitz ◽  
Daniel P. Petrylak ◽  
Jeffrey Holzbeierlein ◽  
Arnauld Villers ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiographic Progression ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Hormone Sensitive ◽  
Over Time

PURPOSE Enzalutamide, a potent androgen-receptor inhibitor, has demonstrated significant benefits in metastatic and nonmetastatic castration-resistant prostate cancer. We evaluated the efficacy and safety of enzalutamide in metastatic hormone-sensitive prostate cancer (mHSPC). METHODS ARCHES (ClinicalTrials.gov identifier: NCT02677896 ) is a multinational, double-blind, phase III trial, wherein 1,150 men with mHSPC were randomly assigned 1:1 to enzalutamide (160 mg/day) or placebo, plus androgen deprivation therapy (ADT), stratified by disease volume and prior docetaxel chemotherapy. The primary end point was radiographic progression-free survival. RESULTS As of October 14, 2018, the risk of radiographic progression or death was significantly reduced with enzalutamide plus ADT versus placebo plus ADT (hazard ratio, 0.39; 95% CI, 0.30 to 0.50; P < .001; median not reached v 19.0 months). Similar significant improvements in radiographic progression-free survival were reported in prespecified subgroups on the basis of disease volume and prior docetaxel therapy. Enzalutamide plus ADT significantly reduced the risk of prostate-specific antigen progression, initiation of new antineoplastic therapy, first symptomatic skeletal event, castration resistance, and reduced risk of pain progression. More men achieved an undetectable prostate-specific antigen level and/or an objective response with enzalutamide plus ADT ( P < .001). Patients in both treatment groups reported a high baseline level of quality of life, which was maintained over time. Grade 3 or greater adverse events were reported in 24.3% of patients who received enzalutamide plus ADT versus 25.6% of patients who received placebo plus ADT, with no unexpected adverse events. CONCLUSION Enzalutamide with ADT significantly reduced the risk of metastatic progression or death over time versus placebo plus ADT in men with mHSPC, including those with low-volume disease and/or prior docetaxel, with a safety analysis that seems consistent with the safety profile of enzalutamide in previous clinical trials in castration-resistant prostate cancer.

scholarly journals Cabazitaxel for Metastatic Castration-Resistant Prostate Cancer: Retrospective Data Analysis from an Indian Centre

2016 ◽  
Vol 9 (2) ◽  
pp. 506-515
Author(s):  
Vanita Noronha ◽  
Amit Joshi ◽  
Vamshi Krishna Muddu ◽  
Vijay Maruti Patil ◽  
Kumar Prabhash
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Retrospective Data Analysis ◽  
Grade 3 ◽  
Named Patient Programme

Objective: To determine the efficacy and safety of cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC) patients from the named patient programme (NPP) at our centre. Methods: mCRPC patients who progressed on docetaxel were given cabazitaxel intravenously every 3 weeks until disease progression or unacceptable toxicity occurred. Overall survival, progression-free survival, prostate-specific antigen response, quality of life (QOL) changes, and safety were reported. Results: Nine men received cabazitaxel (median: 7 cycles; range: 1–27) under the NPP and were followed until death. Median survival was 14.07 months (1.07–23.80) and progression-free survival was 2.67 months (1.07–20.27). QOL was stable for most patients. Common adverse events (grade ≥3) were neutropenia (n = 8), anaemia (n = 4), and leucopenia (n = 4). Conclusion: These data from 9 patients are consistent with the results reported in the TROPIC study with a manageable safety profile.

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.

Comparison of two doses of cabazitaxel plus prednisone in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) previously treated with a docetaxel (D)-containing regimen.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS4692-TPS4692 ◽  
Author(s):  
Mario A. Eisenberger ◽  
Anne-Claire Hardy-Bessard ◽  
Loic Mourey ◽  
Paul N. Mainwaring ◽  
Daniel Ford ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Measurable Disease ◽  
Previously Treated ◽  
Grade 3 ◽  
Ecog Ps

TPS4692^ Background: The phase III TROPIC study (NCT00417079) reported a significant improvement in overall survival (OS) for cabazitaxel (Cbz) + prednisone (P;CbzP) (25 mg/m2 IV Q3W/10 mg PO QD) vs mitoxantrone (M) + P (MP) (median OS 15.1 vs 12.7 mos; HR 0.70; P < 0.0001) in pts with mCRPC (also known as hormone-refractory prostate cancer) previously treated with a D-containing regimen. CbzP is approved by the FDA, EMA and other health authorities for the treatment of pts with mCRPC that has progressed after a D-containing regimen. Cbz toxicity is consistent with other taxanes; compared with M, more hematologic toxicities are reported (primarily Grade 3–4 neutropenia). Phase I/II studies identified 20 and 25 mg/m2 as recommended doses; 25 mg/m2 was selected for the phase III TROPIC study. As pooled data show Grade 3–4 neutropenia incidence is lower with Cbz < 25 mg/m2 (61%) vs ≥ 25 mg/m2 (74%), it is of interest to assess if reducing the Cbz approved dose in mCRPC lessens hematologic toxicity and is non-inferior in terms of efficacy. Methods: PROSELICA (NCT01308580) is a randomized, open-label, multinational, phase III study comparing 20 mg/m2 and 25 mg/m2 Cbz for efficacy and tolerability. Pts with a life expectancy > 6 mos, ECOG PS ≤ 2, histologically/cytologically confirmed metastatic prostate adenocarcinoma resistant to hormone therapy and previously treated with a D-containing regimen are eligible. Pts are randomized 1:1 to receive Cbz 20 mg/m² or 25 mg/m² IV Q3W + P 10 mg PO QD, treated until disease progression, unacceptable toxicity or withdrawal of consent (max 10 cycles), and stratified according to ECOG PS, measurable disease (yes/no) and region. The primary endpoint is OS (non-inferiority design). Secondary endpoints include safety, progression-free survival (PCWG2 criteria), PSA and pain progression and response, tumor response in pts with measurable disease and health-related quality of life. Cbz PK and pharmacogenomics will be assessed in pt subgroups. Planned enrollment is 1,200 pts. Study start was in May 2011; as of Jan 2012, 270 pts had been enrolled. The first DMC meeting recommended continuing the study without change.

Design of the AFFINITY study: A randomized phase III study of a novel clusterin inhibitor, custirsen, plus cabazitaxel/prednisone (CbzP) versus CbzP alone as second-line chemotherapy in metastatic castration-resistant prostate cancer (mCRPC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS5103-TPS5103 ◽  
Author(s):  
Tomasz M. Beer ◽  
Brent A. Blumenstein ◽  
Karim Fizazi ◽  
Sebastien J. Hotte ◽  
Cindy Jacobs ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Disease Progression ◽  
Specific Antigen ◽  
Treatment Resistance ◽  
Phase Iii ◽  
Second Line ◽  
Castration Resistant Prostate Cancer ◽  
Karnofsky Score ◽  
Open Label

TPS5103 Background: Custirsen enhances chemotherapeutic activity via inhibition of clusterin expression. Clusterin is a cytoprotective, antiapoptotic chaperone upregulated by anticancer therapies that confers treatment resistance. In a phase 2 study, mCRPC patients who had progressed within 6 mos of completing first-line docetaxel (DOC)/prednisone (P) and who were retreated with DOC/P and custirsen had a median overall survival of 15.8 mos. Lowering of serum clusterin level during second-line treatment was associated with significantly longer survival. CbzP has recently shown a survival advantage in patients with prostate cancer that has progressed after DOC therapy. The AFFINITY study was designed to evaluate in a larger study whether adding custirsen to CbzP will further improve survival in this patient population. Methods: AFFINITY was initiated in August 2012. Eligible patients in this phase 3, international, multicenter, open-label trial must have received ≥225 mg/m2 of DOC; have progressive disease as defined by RECIST 1.1, bone scan progression, and/or serum prostate-specific antigen level; have metastatic disease of the chest/abdomen/pelvis/bone; have adequate renal and liver function; and have a Karnofsky score ≥70%. Patients may have received up to 1 DOC regimen as well as abiraterone and/or enzalutamide. Approximately 630 patients will receive 21d cycles of Cbz (25 mg/m2IV q21d) + P (10 mg PO/d), either alone or with custirsen 640 mg IV given for 3 loading doses and then weekly until disease progression, unacceptable toxicity, or 10 cycles. The primary efficacy measure is overall survival. The secondary measure is proportion of patients alive without disease progression at Day 140 post-randomization. All efficacy analyses are intent to treat. Adverse events of all patients who receive ≥1 dose of custirsen or Cbz will be included in the safety analysis. This study is sponsored by Teva BPP R&D, Inc., in collaboration with OncoGenex Pharmaceuticals, Inc. Clinical trial information: NCT01578655.

Efficacy and toxicity of q 2 weeks docetaxel versus weekly versus q 3 weeks in metastatic castration-resistant prostate cancer (CRPC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16087-e16087
Author(s):  
Akshiv Malhotra ◽  
Paula Rosenbaum ◽  
Bernard J. Poiesz
Keyword(s):  
Specific Antigen ◽  
Progression Free Survival ◽  
Response Rates ◽  
Test Results ◽  
Castration Resistant Prostate Cancer ◽  
Duration Of Treatment ◽  
Free Survival ◽  
Castration Resistant ◽  
Significant Toxicity ◽  
Number Of Patients

e16087 Background: Standard treatment for metastatic CRPC is docetaxel 75 mg/m2q3weeks. Methods: We retrospectively studied patients treated with q 1, 2, or 3 weeks docetaxel regimens at 30, 60 and 75 mg/m2, respectively. The choice of regimen and duration of treatment was decided by their oncologist. Patients who had been in a clinical trial previously, or treated with any other chemotherapy before docetaxel were excluded. On this basis 41 patients were studied. Prostate specific antigen (PSA) was used as the primary method to assess response and progression. Response was a decline of >/=50% from baseline value with no clinical or radiographic evidence of disease progression. For patients whose PSA did not decrease, progression was a >/= 25% increase from baseline. If the PSA decreased without reaching response criteria, progression was a >/= 25% increase from nadir. In those who responded, progression was a >/= 50% increase from nadir. The increase had to be at least 5ng/ml. Toxicity was graded on the basis of CTCAE version 4.0. Response rate and toxicity in the 3 arms was compared using a two by two square t-test. Results: There were 12, 14 and 15 patients in the q1w, q2w and q3w arms, respectively. Response rates, mean progression free survival (PFS), median PFS, mean overall survival (OS), median OS, mean cumulative dose (MCD) and toxicity are shown in table 1. Toxicity was similar in the q1w, q2w and q3w arms, except grade 1/2 neuropathy was higher in the q2w arm vs. the q1w arm (p=0.005). Conclusions: The MCD, response rates, PFS and OS in the q1w and q3w arms were similar to previously published reports. Patients in the q2w arm received a statistically significant higher MCD. Our data suggest a better outcome in the q2w arm as compared to the q1w and q3w arms. However, given the small number of patients studied, the results are not statistically significant. Toxicity was similar save for grade1/2 neuropathy. [Table: see text]

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]

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