Randomized double-blind, comparative study of abiraterone acetate (AA) plus low-dose prednisone (P) plus androgen deprivation therapy (ADT) versus ADT alone in newly diagnosed, high-risk, metastatic hormone-naive prostate cancer (mHNPC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS5097-TPS5097 ◽  
Author(s):  
Karim Fizazi ◽  
Julie S. Larsen ◽  
Shannon Matheny ◽  
Arturo Molina ◽  
Jinhui Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Gleason Score ◽  
Metastatic Disease ◽  
Localized Prostate Cancer ◽  
Bone Lesions ◽  
Newly Diagnosed ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Androgen Synthesis

TPS5097 Background: Patients (pts) who initially present with metastatic prostate cancer (MPC) (up to 30% of men in Europe; 4% in US) typically progress to metastatic castration-resistant prostate cancer (mCRPC) with a poor prognosis. Prognostic factors impacting survival include high PSA concentration, high Gleason score, high volume of metastatic disease, and bone symptoms. AA decreases testosterone via CYP17 inhibition and is approved for treatment of mCRPC before and after docetaxel-based chemotherapy. Two recent reports (J Clin Oncol. 2012: 30 [suppl. abstr 4521 and 4556]) showed that AA + P in addition to ADT (LHRH agonist) in the neoadjuvant setting led to higher rates of undetectable PSA and complete pathologic response (cPR) or near-cPR in pts undergoing prostatectomy for high risk-localized prostate cancer than with ADT alone, suggesting a potential role for inhibiting extragonadal androgen synthesis prior to emergence of castration-resistance. Because of its benefit in mCRPC, as well as early activity in high risk-localized prostate cancer, AA is being evaluated in high risk mHNPC. Methods: Approximately 1,270 men with newly diagnosed (within 3 months of randomization) high risk mHNPC with at least 2 of 3 high risk factors (≥ 3 bone lesions, presence of visceral metastases or Gleason score ≥ 8) are being randomized to AA 1000 mg + P 5 mg daily + ADT or ADT alone. Pts are stratified by presence of visceral disease and ECOG PS (0-1 vs 2). Distant metastatic disease must be documented by positive bone scan or CT/MRI. ADT or orchiectomy within 3 mos of randomization is allowed. Continued use of anti-androgens after randomization is not allowed on study. The primary endpoint is overall survival. Secondary endpoints include radiographic PFS, time to next skeletal-related event, PSA progression, and subsequent therapy. Two interim analyses and a final analysis are planned. 300 sites from 36 countries will participate. As of February 4, 2013, one patient has entered screening. Clinical trial information: NCT01715285.

Efficacy and safety of abiraterone acetate (AA) and low-dose prednisone (P) in Japanese patients with newly diagnosed, metastatic, hormone-naïve prostate cancer (mHNPC): Subgroup analysis of LATITUDE trial.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 286-286
Author(s):  
Satoshi Fukasawa ◽  
Hiroyoshi Suzuki ◽  
Fuminori Sato ◽  
Katsuyoshi Hashine ◽  
Hisashi Hasumi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Group Versus ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Bone Lesions ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind

286 Background: Patients with high-risk mHNPC have a poor prognosis. In Japan, mHNPC accounts for approximately 10% of newly diagnosed prostate cancers. AAP was approved for the treatment of castration-resistant prostate cancer in Japan in July 2014. We now report the clinical benefit of AAP with ADT in Japanese patients with newly diagnosed, high-risk mHNPC. Methods: Interim analysis of the multinational, randomized, double-blind, placebo-controlled, phase 3 study, LATITUDE, was previously reported at ASCO2017. We evaluated the superiority of AA 1g + P 5 mg + ADT (AAP group) to ADT+PBOs of AA and P (P group) in mHNPC with ≥ 2 of 3 risk factors (Gleason ≥ 8, ≥ 3 bone lesions, measurable visceral metastases) for the subgroup of Japanese patients. Results: Of 1199 total patients in LATITUDE trial, 70 patients were Japanese (AAP group, n = 35; P group, n = 35). The hazard ratio (HR) for overall survival in the AAP group versus the P group was 0.635 (95% confidence interval [CI], 0.152 to 2.659) and HR for radiographic progression-free survival was 0.219 (95%CI, 0.086 to 0.560). The incidence of adverse events (AE) was 97% (34/35) in both groups. AEs that occurred in the AAP group at a frequency ≥10% compared with the P group included hypertension, hypokalemia, rib fracture, hematuria and hyperbilirubinemia. The incidence of Grade 3 and 4 AEs was 66% in the AAP group and 20% in the P group. As a whole, efficacy and safety of Japanese patients in LATITUDE were shown to be consistent with those of overall population. Conclusions: AAP has shown a favorable risk/benefit balance and may serve as a new treatment option to improve the prognosis of Japanese mHNPC patients with high-risk prognostic factors. Clinical trial information: NCT01715285.

LATITUDE: A phase III, double-blind, randomized trial of androgen deprivation therapy with abiraterone acetate plus prednisone or placebos in newly diagnosed high-risk metastatic hormone-naive prostate cancer.

2017 ◽  
Vol 35 (18_suppl) ◽  
pp. LBA3-LBA3 ◽  
Author(s):  
Karim Fizazi ◽  
Namphuong Tran ◽  
Luis Enrique Fein ◽  
Nobuaki Matsubara ◽  
Alfredo Rodríguez Antolín ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Early Intervention ◽  
High Risk ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Bone Lesions ◽  
Newly Diagnosed ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
End Points

LBA3 Background: Pts with newly diagnosed mHNPC, particularly with high-risk characteristics, have a poor prognosis. ADT+docetaxel showed improved outcomes in mHNPC, but many pts are not candidates for docetaxel and may benefit from alternative therapy. AA+P is indicated for metastatic castration-resistant prostate cancer pts. LATITUDE evaluates clinical benefit of early intervention with AA+P added to ADT in newly diagnosed, high-risk mHNPC pts. Methods: 1199 pts with newly diagnosed (≤ 3 mos prior to randomization) mHNPC (ECOG PS 0-2) with ≥ 2 of 3 risk factors (Gleason ≥ 8, ≥ 3 bone lesions, measurable visceral metastases) were randomized 1:1 to ADT+AA (1 g QD) + P (5 mg QD) or ADT+PBOs of AA and P. Co-primary end points were overall survival (OS) and radiographic progression-free survival (rPFS). One rPFS (~565 events), 2 interim, and 1 final OS analyses (~426, ~554, and ~852 events) were planned. Results: At this first interim analysis (median follow-up of 30.4 mos; 406 deaths [48%]; 593 rPFS events), OS, rPFS, and all secondary end points significantly favored ADT+AA+P (Table). The IDMC unanimously recommended unblinding the study and crossing pts to ADT+AA+P. Grade 3/4 adverse events (ADT+AA+P vs ADT+PBOs) (%): hypertension (20.3 vs 10.0); hypokalemia (10.4 vs 1.3); increased ALT (5.5 vs 1.3) or AST (4.4 vs 1.5). Conclusions: Early use of AA+P added to ADT in pts with high-risk mHNPC yielded significantly improved OS, rPFS, and all secondary end points vs ADT+PBOs alone. ADT+AA+P had a favorable risk/benefit ratio and supports early intervention with AA+P in newly diagnosed, high-risk mHNPC. Clinical trial information: NCT01715285. [Table: see text]

scholarly journals Circulating Tumor Cells as a Marker of Disseminated Disease in Patients with Newly Diagnosed High-Risk Prostate Cancer

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 160 ◽  
Author(s):  
Wojciech A. Cieślikowski ◽  
Joanna Budna-Tukan ◽  
Monika Świerczewska ◽  
Agnieszka Ida ◽  
Michał Hrab ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Disease ◽  
Newly Diagnosed ◽  
High Risk Prostate Cancer ◽  
Intergroup Comparison ◽  
Risk Prostate Cancer

The aim of this study was to investigate whether the enumeration of circulating tumor cells (CTCs) in blood can differentiate between true localized and metastatic prostate cancer. A cross-sectional study of 104 prostate cancer patients with newly diagnosed high-risk prostate cancer was conducted. In total, 19 patients presented metastatic disease and 85 were diagnosed with localized disease. Analyses included intergroup comparison of CTC counts, determined using the CellSearch® system, EPISPOT assay and GILUPI CellCollector®, and ROC analysis verifying the accuracy of CTC count as a maker of disseminated prostate cancer. The vast majority (94.7%) of patients with advanced-stage cancer tested positively for CTCs in at least one of the assays. However, significantly higher CTC counts were determined with the CellSearch® system compared to EPISPOT assay and GILUPI CellCollector®. Identification of ≥4 CTCs with the CellSearch® system was the most accurate predictor of metastatic disease (sensitivity 0.500; specificity 0.900; AUC (95% CI) 0.760 (0.613–0.908). Furthermore, we tried to create a model to enhance the specificity and sensitivity of metastatic prediction with CTC counts by incorporating patient’s clinical data, including PSA serum levels, Gleason score and clinical stage. The composite biomarker panel achieved the following performance: sensitivity, 0.611; specificity, 0.971; AUC (95% CI), 0.901 (0.810–0.993). Thus, although the sensitivity of CTC detection needs to be further increased, our findings suggest that high CTC counts might contribute to the identification of high-risk prostate cancer patients with occult metastases at the time of diagnosis.

Detecting circulating tumor cells (CTCs) in patients with high-risk, localized prostate cancer using the CellSearch platform.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15178-e15178
Author(s):  
Sumanta Kumar Pal ◽  
Clayton Lau ◽  
Miaoling He ◽  
Przemyslaw Twardowski ◽  
Timothy G. Wilson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Gleason Score ◽  
Prognostic Value ◽  
Localized Prostate Cancer ◽  
Cellsearch System ◽  
Mesenchymal Transition ◽  
E Cadherin

e15178 Background: Enumeration of circulating tumor cells (CTCs) using the CellSearch platform has prognostic value in patients with metastatic castration resistant prostate cancer. However, the prognostic value of CTC enumeration in high-risk, localized prostate cancer (HRLPC) remains undefined. Methods: Patients with HRLPC (defined by ≥1 of the following criteria: ≥ cT3a disease, Gleason score 8-10, or PSA > 20 ng/mL) who have chosen prostatectomy for their definitive management were prospectively identified. Patients were consented to receive 4 sequential 30 mL blood draws, each collected in 3 separate 10 mL EDTA tubes. The first 2 blood draws were conducted 2 weeks prior and immediately prior to surgery, while the second 2 blood draws were conducted 4-6 weeks and 3 months following surgery. Within 4 hrs of blood collection, the white blood cell (WBC) fraction was pooled and Ficoll purified. The WBC fraction was transferred to a CellSave tube, and CTCs were enumerated using the CellSearch system. Expression of CD133 and E-cadherin was characterized using the CellSearch system in patients with detectable CTCs. Results: Within 3 monthsof study initiation in Nov 2011, 19 of a planned 37 patients have been accrued. Median age in the cohort was 65 (range, 51-74), and the number of patients with Gleason score 8-10, ≥ cT3a disease, or PSA > 20 ng/mL was 16, 4, and 2, respectively. The majority of patients (17/19, or 89%) had only one high-risk feature. Mean baseline PSA for the cohort was 11.4 (range, 3.4-37). CTCs were detectable in 67% of patients prior to surgery, 27% of patients at 1 month following surgery and 67% of patients at 3 months following surgery. Amongst those patients with detectable CTCs, the median count was 3 (range, 1-7). Further, in these patients, CD133 and E-cadherin were detected in 44% and 46% of specimens assessed, respectively. Full details of these analyses will be provided at the time of the meeting. Conclusions: Using a modified methodology, CTC enumeration using the CellSearch platform is feasible in patients with HRLPC. Interestingly, markers of epithelial-mesenchymal transition and stem cell lineage are detectable in a proportion of patients with localized disease.

Charlson Score as prognostic factor in patients with castration-resistant prostate cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 242-242 ◽  
Author(s):  
Gustavo Jankilevich ◽  
Luciana Gennari ◽  
Matias Salazar ◽  
Claudio Graziano ◽  
Eduardo Saravia ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Gleason Score ◽  
Cox Regression ◽  
Independent Predictor ◽  
Performance Status ◽  
Univariate Analysis ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance

242 Background: Tumor stage, Gleason score, PSA, Performance Status have been identified as important predictors of survival in prostate cancer. The Charlson Comorbidity Index (CCI) is a validated score used to stratify patients according to comorbidities. To evaluate the prognostic role of CCI in patients with CPRC. Methods: A retrospective study based on an analysis of medical records of 212 patients with CRPC treated at Durand Hospital between 2010-2015. The CCI was calculated for each patient and a correlation with overall survival was performed. Statistical analysis included univariate analysis and multivariate analysis (Cox regression). Patients were stratified according CCI ≤ 7.6 or ≥ 7.6. Survival analysis was performed using the Kaplan-Meier curve. Results: We analyzed records of 212 patients with prostate cancer, of which 59 were resistant to castration. Median age 69 years, the PFS with androgen blockade was 32.4 months. Patients with CPRC 54% perform chemotherapy as first-line treatment of castration resistance and 46% performed treatment of hormonal manipulation (Enzalutamide or Abiraterone Acetate). Median overall survival of patients with CCI < 7.6 was 75 months versus 62 months for those with CCI > 7.6 HR: 1.19 (1.03 to 1.36) p: 0.01. In multivariate analysis the ICC was an independent predictor of mortality in these patients HR: 1.23 (1.03 to 1.48) p: 0.02. (Table 1) CCI ≤ 7,6 was predictor to subsequent lines in CPRC setting. Gleason score, PS were independent predictors of survival. Conclusions: Based on our results we can consider the CCI as an independent predictor of survival in CPRC patients. CCI could be an useful tool useful to select patients in clinical trial and community settings. [Table: see text]

Castration resistance and high-risk disease among nonmetastatic (M0) prostate cancer (PC) patients on androgen deprivation therapy (ADT).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1581-1581
Author(s):  
Melissa Pirolli ◽  
Rohini Khorana Hernandez ◽  
Karynsa Cetin ◽  
Jane Quigley ◽  
Yanina Grant-Huerta ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Specific Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Real World Data ◽  
Adult Men ◽  
Increased Risk ◽  
Main Driver ◽  
Definition Of

1581 Background: Prostate-specific antigen (PSA) is a well-known PC biomarker. In the M0 setting, rising PSAs despite ADT is an indication of the development of castration-resistant prostate cancer (CRPC). In this disease state, men are at risk for developing bone metastasis (BM), which is associated with significant morbidity and may negatively affect survival. Using real-world data, we explored PSA-based criteria to identify patients who develop CRPC while on ADT and the subsets that may be at increased risk of BM. Methods: We used the Oncology Services Comprehensive Electronic Records (OSCER) database, which includes electronic medical record (EMR) data on cancer patients from 328 urology and oncology clinics in the US. Eligible patients were adult men with M0 PC with ≥1 PSA recorded between 3/1/2010 and 2/28/2011 and currently receiving ADT (gonadotropin-releasing hormone agonists or bilateral orchiectomy) for ≥6 months (mos). We defined CRPC as two sequential PSA rises while on ADT and high risk for BM as any PSA ≥8 ng/mL or PSA doubling time (DT) ≤10 mos, as described by Smith MR et al, Lancet 2012. We explored subsets of CRPC patients who may be at even higher risk of BM using PSA thresholds (≥8 ng/mL and ≥20 ng/mL) and DT (≤4, 6, 8, and 10 mos). Results: Of 1,818 men with M0 PC receiving ADT ≥6 mos, 36% (N=646) met the CRPC definition, of whom 80% (N=517) had PSA ≥8 ng/mL and/or PSA DT ≤10 mos (high risk). PSA DT alone explained 63% (44% / 70%) to 93% (65% / 70%) of subgroup eligibility (Table), and emerged as a main driver in defining increased risk of BM for CRPC subsets. Conclusions: In this analysis of EMR data, over one-third of men with M0 PC on ADT met criteria for CRPC, and most CRPC patients (80%) may be considered at high risk for BM. Requiring ≥3 PSAs to define CRPC may be a limitation; however, because PSAs are closely monitored in patients on ADT, these definitions of CRPC and high risk may be useful in practice. These data suggest that PSA DT may be a more clinically meaningful measure of defining CRPC subsets than absolute PSA thresholds. [Table: see text] .

Time to next line therapy after initiation of sipuleucel-T in metastatic castration-resistant prostate cancer patients.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 341-341
Author(s):  
Dai Luu ◽  
Leanne Goldstein ◽  
Przemyslaw Twardowski
Keyword(s):  
Prostate Cancer ◽  
Median Time ◽  
Gleason Score ◽  
Metastatic Disease ◽  
Mixed Model ◽  
Phase Iii ◽  
Karnofsky Performance Score ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Line Therapy

341 Background: Sipuleucel-T is an autologous cellular immunotherapy approved for patients with symptomatic or minimally asymptomatic metastatic castration-resistant prostate cancer based on prolongation of overall survival. We sought to retrospectively analyze the type and time to next-line therapy after the initiation of Sipuleucel-T (Sip-T) in the era of multiple new other therapeutic compounds that became available since approval of Sip-T to better understand the context of utilization of this immunotherapy in the current era. Methods: We performed a retrospective analysis of 53 patients with metastatic prostate cancer (PC) who have been treated with Sip-T at The City of Hope Medical Center between September 2010 and April 2013 and subsequently received another therapy. Variables included age at Sip-T treatment, Karnofsky Performance Score (KPS), Gleason score at diagnosis, extent of metastatic disease (limited or extensive), and white blood cell (WBC) count pre and post (Sip-T). PSA was measured at six time points (3 pre and 3 post Sip-T) and these were analyzed using a mixed linear regression model. A Cox Proportional Hazard model was used to examine predictors of time in days to next therapy as a function of the above variables including mixed model slopes of PSA. Results: Kaplan – Meier estimated median time to next treatment among the 53 patients was 122 days (95% CI, 86-177 days) and was significantly predicted by slope of PSA from the mixed model (HR = 25.883, p < .0001), WBC post therapy (HR = 1.352, p = 0.0017), and age at Sip-T (HR = 1.044 p = 0.0492). KPS, Gleason score, pre Sip-T WBC, and the extent of metastatic disease were not predictive. Most patients had abiraterone acetate for next treatment (n = 32, 58.2%). Other treatments included docetaxel (n = 5, 9.1%), orteronel with prednisone or prednisone alone (n = 12, 21.8%), and others (n = 6, 10.9%). Conclusions: In our experience median time to subsequent therapies was shorter than reported in pivotal Phase III study. Shorter time to post-Sip-T therapy was associated with older age, higher levels of WBC post-Sip-T therapy and more rapid rate of increase in the PSA level.

scholarly journals Novel Strategies for Treating Castration-Resistant Prostate Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 339
Author(s):  
David Ka-Wai Leung ◽  
Peter Ka-Fung Chiu ◽  
Chi-Fai Ng ◽  
Jeremy Yuen-Chun Teoh
Keyword(s):  
Prostate Cancer ◽  
Metastatic Disease ◽  
Advanced Prostate Cancer ◽  
Imaging Techniques ◽  
Treatment Strategies ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Management Options ◽  
Castration Resistant

The development of castration resistance is an inevitable pathway for the vast majority of patients with advanced prostate cancer. Recently, there have been significant breakthroughs in the understanding and management options of castration-resistant prostate cancer. Three novel hormonal agents showed survival benefits in non-metastatic patients. As for metastatic disease, there was an even wider range of management options being investigated. This review summarized advances in the management of castration-resistant prostate cancer (CRPC) including emerging data on novel imaging techniques and treatment strategies.

Sign in / Sign up

Export Citation Format

Share Document