Characteristics of Chinese patients with advanced prostate cancer: A muliticentre, non-interventional, observational, prospective, registry study of docetaxel.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 328-328
Author(s):  
Dalin He ◽  
Zhongquan Sun ◽  
Jianming Guo ◽  
Zhigen Zhang ◽  
Yuxi Shan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Progression ◽  
Disease Progression ◽  
Remission Rate ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Chinese Patients ◽  
Second Line ◽  
Registry Study ◽  
First Line

328 Background: Prostate cancer (PC) is the second most frequently diagnosed malignancy in males worldwide, and stands in 7th place among malignancies in Chinese males. This study investigated the real-world treatment patterns of docetaxel as chemotherapy in patients with advanced PC in China. Methods: This was a multi-center, prospective, observational, non-interventional, product registry study. All patients with advanced PC who failed with previous endocrine therapies, were receiving docetaxel containing chemotherapy, and consented to participate in the study were eligible to be enrolled. Patients were followed-up 2 years, for the collection and analysis of data on docetaxel treatment mode, prostate specific antigen (PSA) remission rate, survival time, etc. Results: A total of 407 patients were enrolled from Aug 2011 through Jun 2014, with a mean Gleason score of 8.0 (SD: 1.11), and median PSA of 61.0 (range: 0.0 to 5000.0) ng/ml. 302 (74.2%) patients were classified as clinical stage IV. For Eastern Cooperative Oncology Group (ECOG) score, 145 (35.6%), 205 (50.4%), 48 (11.8%), patients had scores of 0, 1, 2, respectively. Metastasis to bone was present in 340 (83.5%) patients; metastasis to other organs (liver, lungs, adrenal glands, brain, etc.) was present in 57 (14.0%) patients. Last disease progression prior to enrolment was evidenced by tumor progression in 132 (32.4%) patients and by PSA elevation in 379 (93.1%) patients. 173 (43.0%) and 120 (29.9%) patients started docetaxel therapy after failure of the first line and second line endocrine therapies, respectively; 51 (12.7%) patients after failure of the third line or more endocrine therapies. Conclusions: This abstract presented characteristics of Chinese patients with advanced PC revealed by a Chinese PC study, which indicated Chinese patients were in later stage and higher risk compared with their western counterparts. The majority of patients started docetaxel therapy after failure of first line and second line endocrine therapies. PSA elevation and tumor progression were the 2 main causes that Urologists determined for disease progression. Clinical trial information: no registration number.

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.

A randomized study of enzalutamide in patients with localized prostate cancer undergoing active surveillance (ENACT).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS5097-TPS5097
Author(s):  
Neal D. Shore ◽  
Srinivas Vourganti ◽  
Jonathan L. Silberstein ◽  
Bruce A. Brown ◽  
Samuel Wilson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Disease Progression ◽  
Active Surveillance ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Pharmacological Intervention ◽  
Intermediate Risk ◽  
Open Label ◽  
Group Status ◽  
End Points

TPS5097 Background: Prostate cancer (PC) patients (pts) who select active surveillance (AS) are a heterogeneous population with varying risks for disease progression. Studies have estimated that approximately 31–42% of pts electing AS have experienced disease progression (pathological or therapeutic) over 1.8 and 2.3 years. There is no evidence-based pharmacological intervention which has effectively lessened this progression event. Pharmacological intervention with enzalutamide (ENZ), an androgen receptor inhibitor approved for treatment of metastatic castration-resistant PC, may lessen this progression. The aims of this study are to evaluate the efficacy of ENZ versus AS alone for delaying time to progression in pts with clinically localized PC undergoing AS. This study examines the effects of ENZ on progression in a subset of pts with low- or intermediate-risk PC who would otherwise elect an AS protocol. Methods: This is a multicenter, randomized, open-label study (NCT02799745). Eligibility criteria include histologically confirmed prostate adenocarcinoma within 6 months of screening, low or intermediate risk PC (T1c−T2c, prostate-specific antigen [PSA] < 20, N0, M0, Gleason score ≤7 [3+4 pattern only]), Eastern Cooperative Oncology Group status ≤2 and estimated life expectancy > 5 years. Exclusion criteria include any prior PC intervention. Pts will be randomized to receive open-label oral ENZ 160 mg/day once daily or to AS during the 1-year study treatment period. After the first year, all pts will be followed for one additional year with no other intervention. All pts will undergo prostate biopsy at 1 and 2 years. The primary end point is time to PC progression (pathological or therapeutic). Secondary end points include safety, incidence of negative biopsies for cancer at 1 and 2 years, percentage of cancer positive cores at 1 and 2 years, time to PSA progression, incidence of secondary rise in serum PSA, and quality-of-life questionnaires. Exploratory end points include biomarker assessment and genomic analysis. Study enrolment commenced in June 2016, with study completion expected in March 2019. Planned total enrolment is 222 pts from ~60 United States/Canadian sites. Clinical trial information: NCT02799745.

Pain palliation as an oncology label indication: Lessons learned in custirsen phase III development.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 222-222
Author(s):  
Tomasz M. Beer ◽  
Sebastien J. Hotte ◽  
Johann Sebastian De Bono ◽  
Philippe Beuzeboc ◽  
Nashat Y. Gabrail ◽  
...  
Keyword(s):  
Disease Progression ◽  
Opioid Analgesic ◽  
Specific Antigen ◽  
Phase Iii ◽  
Second Line ◽  
Pain Palliation ◽  
First Line ◽  
Analgesic Regimen ◽  
Analgesic Use ◽  
Label Indication

222 Background: Durable pain palliation (dPP) in metastatic castrate-resistant prostate cancer (mCRPC) is a measure of clinical benefit suitable for a label indication. A randomized, double-blind, placebo-controlled, phase III study developed with FDA under a Special Protocol Assessment (SPA) compared custirsen/taxane (cust/tax) to placebo/taxane (plac/tax) as second-line chemotherapy for patients (pts) with mCRPC with disease progression during or after first-line docetaxel. Primary efficacy was 12-week or more dPP. Other endpoints included overall survival (OS), serious adverse events (AEs), and ≥Gr 3 AEs. Methods: Patients were randomized (1:1) to second-line taxane (docetaxel retreatment or cabazitaxel; based on prior docetaxel response, progression) + 640 mg custirsen or placebo. Eligible pts had to have baseline stable pain on consistent opioid-analgesic regimen. With a one-sided alpha of 0.025, power of 90%, and estimated difference in proportion of 25% vs. 10% dPP, the trial required 292 pts. Results: Trial was activated at a total of 62 sites and was stopped after 20 months (mo) with only 35 pts screened/14 pts enrolled. Requirements for baseline stable pain/analgesic use proved too restrictive to complete enrollment. Demographics were comparable. Prior response to first-line docetaxel occurred in 93% pts. Disease progression after first-line docetaxel based on bone scan (n=10) or prostate-specific antigen (n=4); median time from end of first-line to progression one mo. Treatment of a median thre cycles plac/tax arm compared to six cycles cust/tax arm. Three pts achieved dPP (n=1 [14%] plac/tax; n=2 [29%] cust/tax). Median OS (95% CI) was 7.8 (3.2, 11.5) mo plac/tax vs. 11.8 (9.8, 15.7) mo cust/tax. AEs greater than or equal to Gr 3 reported for two pts or more included: back pain (0 plac/tax; 2 cust/tax), hyperesthesia (0,2), asthenia (2,1). Serious AEs reported for nine subjects (4,5). Only serious AE reported in more than 1 pt was hyperesthesia, leading to study discontinuation (0, 2). Conclusions: Enrollment was not feasible due to restrictive trial criteria of stable baseline pain/consistent analgesia, which were too difficult to achieve. Thus, a survival based study has been launched and is recruiting, with monitoring of pain/analgesic use. Pragmatic criteria for oncology pain studies are needed. Clinical trial information: NCT01083615.

Complete androgen blockade as second-line hormone manipulation and delay of chemotherapy in metastatic prostate cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16141-e16141
Author(s):  
R. Kaliks-Guendelmann ◽  
P. Santi ◽  
A. Cardoso ◽  
A. Del Giglio
Keyword(s):  
Prostate Cancer ◽  
Clinical Benefit ◽  
Metastatic Prostate Cancer ◽  
Specific Antigen ◽  
Second Line ◽  
Clinical Predictors ◽  
First Line ◽  
Complete Androgen Blockade ◽  
Androgen Blockade

e16141 Background: Complete androgen blockade (CAB) after failure of castration or androgen receptor blocker (ARB) has not shown to prolong survival in patients with metastatic prostate cancer, unlike docetaxel-based chemotherapy. The widely variable clinical benefit seen with CAB as second-line hormone manipulation still justifies the identification of the patients to whom it should be offered. Objective: to evaluate progression-free survival (PFS) and overall survival (OS) in patients treated with CAB after failure of castration or ARB and to identify clinical predictors of benefit. Methods: We performed a retrospective analysis of all patients with metastatic prostate cancer treated with CAB as second-line hormone manipulation in a single institution after September 2005. OS and PFS were estimated using Kaplan-Meyer plots. We identified 78 patients and evaluated correlations of prostate specific antigen (PSA), Gleason scores, age, type and length of first-line hormone manipulation with OS and PFS during CAB. Fifty-four patients had failed castration and 24 had failed ARB. Forty-four patients received chemotherapy after failing CAB. Results: With a median follow-up of 21 months, median PFS with CAB was 12 months (CI 6.8–17.2). We did not find any correlation of PFS with type of first-line hormone manipulation (castration vs ARB, p = 0.10), age group (≤70 or >70 years old, p = 0.10), level of PSA at diagnosis (≤50 or >50 ng/mL, p = 0.17) or length of first-line hormone manipulation (≤14m vs >14 m, p = 0.78). There was no significant correlation between PFS and Gleason score at diagnosis (score ≤7 or >7, p = 0.25), nor between the level of testosterone at the beginning of CAB and PFS. Median OS for patients on CAB after failing castration was 36 months (CI 24–48), and median OS of patients on chemotherapy was not reached at 9.5 months follow-up. Conclusions: Based on a PFS of 12 months, OS of 36 months and good patient tolerance, we believe CAB should still be used in CRPC, prior to initiation of chemotherapy. Predictors of clinical benefit are still to be identified. No significant financial relationships to disclose.

Enzalutamide plus androgen deprivation therapy (ADT) versus flutamide plus ADT in men with castration-resistant prostate cancer (CRPC): AFTERCAB.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 81-81
Author(s):  
Hiroji Uemura ◽  
Kazuki Kobayashi ◽  
Akira Yokomizo ◽  
Shiro Hinotsu ◽  
Shigeo Horie ◽  
...  
Keyword(s):  
Group Performance ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Disease Stage ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Psa Progression

81 Background: Enzalutamide has been approved for the treatment of CRPC in Japan since 2014. This study compared the efficacy and safety of enzalutamide + ADT and flutamide + ADT in the treatment of men with CRPC who progressed despite combined androgen blockade with bicalutamide + ADT. The sequential order of treatment was also investigated. Methods: The open-label, Phase 4 AFTERCAB study (NCT02918968) was conducted from November 2016–March 2020 in Japanese men aged ≥20 years with asymptomatic or mildly symptomatic CRPC (metastatic or nonmetastatic) and an Eastern Cooperative Oncology Group performance status of 0 or 1 who progressed despite bicalutamide + ADT. Patients were initially randomized to enzalutamide (160 mg/day) + ADT (enzalutamide first) or flutamide (375 mg/day [125 mg 3 × daily]) + ADT (flutamide first) as first-line therapy. Following prostate-specific antigen (PSA) progression, other disease progression, or discontinuation of first-line therapy due to an adverse event (AE), patients switched to the other treatment as second-line therapy. The primary endpoint was time to PSA progression with first-line therapy (TTPP1). Secondary endpoints included TTPP2 (TTPP1 + time to PSA progression with second-line therapy). AEs were monitored to assess safety. Results: 206 men were randomized, stratified by study site and disease stage. Baseline demographics and disease characteristics were similar between treatment arms. Median treatment exposure was 14.3 months (range 0.8–35.9) with enzalutamide first and 5.6 months (range 0.3–37.7) with flutamide first. 133 patients transitioned to second-line therapy (n=48 for enzalutamide first and n=85 for flutamide first). TTPP1 was significantly improved with enzalutamide first versus flutamide first; numerically longer TTPP2 was observed with enzalutamide first versus flutamide first (Table). With first-line therapy, 92.2% (n=94) of patients reported treatment-emergent AEs (TEAEs) and 28.4% (n=29) reported serious TEAEs for enzalutamide first. Corresponding numbers for flutamide first were 76.0% (n=79) for TEAEs and 14.4% (n=15) for serious TEAEs. Conclusions: Treatment with enzalutamide + ADT provided a significant improvement in time to PSA progression versus flutamide + ADT as first-line therapy. Both treatments were generally well tolerated, with AEs consistent with the known safety profiles. Clinical trial information: NCT02918968. [Table: see text]

scholarly journals A prognostic model for stratifying clinical outcomes in chemotherapy-naive metastatic castration-resistant prostate cancer patients treated with abiraterone acetate

2017 ◽  
Vol 12 (2) ◽  
pp. E47-52 ◽  
Author(s):  
Daniel Joseph Khalaf ◽  
Claudia M. Avilés ◽  
Arun A. Azad ◽  
Katherine Sunderland ◽  
Tilman Todenhöfer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcomes ◽  
Group Performance ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Prognostic Index ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Progression

Introduction: Recently, a prognostic index including six risk factors (RFs) (unfavourable Eastern Cooperative Oncology Group performance status [ECOG PS], presence of liver metastases, short response to luteinizing hormone-releasing hormone [LHRH] agonists/ antagonists, low albumin, increased alkaline phosphatase [ALP] and lactate dehydrogenase [LDH]) was developed from the COUAA- 301 trial in post-chemotherapy metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate. Our primary objective was to evaluate this model in a cohort of chemotherapy-naive mCRPC patients receiving abiraterone.Methods: We identified 197 chemotherapy-naive patients who received abiraterone at six BC Cancer Agency centres and who had complete information on all six RFs. Study endpoints were prostate-specific antigen (PSA) response rate (RR), time to PSA progression, time on treatment, and overall survival (OS). PSA RR and survival outcomes were compared using Χ2 test and log-rank test. Multivariable Cox proportional hazard analysis was performed to identify RFs independently associated with OS.Results: Patients were classified into good (0‒1 RFs), intermediate (2‒3 RFs), and poor (4‒6 RFs) prognostic groups (33%, 52%, and 15%, respectively). For good-, intermediate-, and poor-risk patients, PSA RR (≥50% decline) was 60% vs. 42% vs. 40% (p=0.05); median time to PSA progression was 7.3 vs. 5.3 vs. 5.0 months (p=0.02); and median OS was 29.4 vs. 13.8 vs. 8.7 months (p<0.0001).Conclusions: The six-factor prognostic index model stratifies clinical outcomes in chemotherapy-naive mCRPC patients treated with abiraterone. Identifying patients at risk of poor outcome is important for informing clinical practice and clinical trial design.

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