scholarly journals Long term efficacy and QOL data of chemohormonal therapy (C-HT) in low and high volume hormone naïve metastatic prostate cancer (PrCa): E3805 CHAARTED trial

2016 ◽  
Vol 27 ◽  
pp. vi244 ◽  
Author(s):  
C. Sweeney ◽  
Y.-H. Chen ◽  
G. Liu ◽  
M. Carducci ◽  
D. Jarrard ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
High Volume ◽  
Chemohormonal Therapy ◽  
Term Efficacy

Androgen deprivation therapy (ADT) plus docetaxel (D) versus ADT alone for hormone-naïve metastatic prostate cancer (PCa): Long-term analysis of the GETUG-AFU 15 phase III trial.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 140-140 ◽  
Author(s):  
Gwenaelle Gravis ◽  
Jean-Marie Boher ◽  
Florence Joly ◽  
Stephane Oudard ◽  
Laurence Albiges ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
High Volume ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Intention To Treat ◽  
Original Analysis ◽  
Definition Of

140 Background: ADT is standard treatment for metastatic PCa. Recently, the E3805 trial reported a survival benefit for (ADT+D) in high volume disease (HVD) patients, whereas the GETUG-15 trial did not demonstrate a survival improvement among a less selected group of patients (pts) with hormone-naïve metastatic PCa. We report an updated analysis of overall survival (OS) of the GETUG 15 trial and aligned the definition of HVD and low volume disease (LVD) subgroups. Methods: Long-termOS was analyzed in the intention-to-treat population (n=385 pts). Additionally, we retrospectively assessed the tumor volume as defined per E3805criteria in all patients enrolled in GETUG 15. Results: See Table. With a median follow-up of 82.9 months (95%CI [80.5-84.3]) (vs 50 months (95%CI [80.5-84.3] in the original analysis), 212 patients (55%) have died. The median OS is 46.5 [39.1-60.6] and 60.9 months [46.1-71.4] in the ADT and in the ADT + D arms, respectively (HR: 0.9 [95%CI: 0.7-1.2]). In HVD patients (n=183, 47.5%), median OS rates were 35.1 months [29.9-44.2] in the ADT alone arm and 39 months [28-52.6] in the ADT+D arm (HR: 0.8 [0.6-1.2]). Conclusions: With longer follow-up, the addition of docetaxel to ADT did not significantly improve OS in patients with hormone-naïve metastatic prostate cancer. In the retrospective analysis using aligned definition of volume of metastasis as E3805, the HVD outcomes were similar to E3805 for ADT alone and there was a non-significant 4 months increase in OS with ADT+D, in this underpowered subset. Clinical trial information: 00104715. [Table: see text]

647 PHASE 1–2 STUDY OF MDV3100 IN PRE- AND POST-DOCETAXEL ADVANCED PROSTATE CANCER: LONG-TERM EFFICACY RESULTS

2011 ◽  
Vol 185 (4S) ◽  
Author(s):  
Celestia Higano ◽  
Tomasz Beer ◽  
Evan Yu ◽  
Mary-Ellen Taplin ◽  
Eleni Efstathiou ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Phase 1 ◽  
Term Efficacy

scholarly journals Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial

2018 ◽  
Vol 36 (11) ◽  
pp. 1080-1087 ◽  
Author(s):  
Christos E. Kyriakopoulos ◽  
Yu-Hui Chen ◽  
Michael A. Carducci ◽  
Glenn Liu ◽  
David F. Jarrard ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Volume ◽  
Phase Iii ◽  
Cancer Trial ◽  
Term Survival ◽  
Chemohormonal Therapy ◽  
Androgen Ablation ◽  
Hormone Sensitive ◽  
Low Volume

Purpose Docetaxel added to androgen-deprivation therapy (ADT) significantly increases the longevity of some patients with metastatic hormone-sensitive prostate cancer. Herein, we present the outcomes of the CHAARTED (Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) trial with more mature follow-up and focus on tumor volume. Patients and Methods In this phase III study, 790 patients with metastatic hormone-sensitive prostate cancer were equally randomly assigned to receive either ADT in combination with docetaxel 75 mg/m2 for up to six cycles or ADT alone. The primary end point of the study was overall survival (OS). Additional analyses of the prospectively defined low- and high-volume disease subgroups were performed. High-volume disease was defined as presence of visceral metastases and/or ≥ four bone metastases with at least one outside of the vertebral column and pelvis. Results At a median follow-up of 53.7 months, the median OS was 57.6 months for the chemohormonal therapy arm versus 47.2 months for ADT alone (hazard ratio [HR], 0.72; 95% CI, 0.59 to 0.89; P = .0018). For patients with high-volume disease (n = 513), the median OS was 51.2 months with chemohormonal therapy versus 34.4 months with ADT alone (HR, 0.63; 95% CI, 0.50 to 0.79; P < .001). For those with low-volume disease (n = 277), no OS benefit was observed (HR, 1.04; 95% CI, 0.70 to 1.55; P = .86). Conclusion The clinical benefit from chemohormonal therapy in prolonging OS was confirmed for patients with high-volume disease; however, for patients with low-volume disease, no OS benefit was discerned.

scholarly journals Future therapeutic strategies for metastatic prostate cancer

2019 ◽  
Vol 9 (6-7) ◽  
pp. 117-130 ◽  
Author(s):  
Minke Smits ◽  
Winald Gerritsen ◽  
Niven Mehra
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Predictive Biomarkers ◽  
Parp Inhibition ◽  
Oncological Patient ◽  
Damage Repair ◽  
Repair Deficiency ◽  
Disease Stabilization ◽  
Combination Regimens

Abstract During the last decade several new therapies have been investigated and approved for metastatic prostate cancer that greatly impacts patients’ quality of life and outcome. Nevertheless, optimal sequencing algorithms are still lacking, as are combinatory strategies that deliver long-term disease stabilization. Precision medicine, utilizing molecular profiles from tissue biopsies, will help us deliver optimal patient care by identifying patients that may benefit from targeted- and immunotherapy, and help guide treatment decisions by use of predictive biomarkers. Here, we present an overview of predictive biomarkers in prostate cancer, including mismatch repair and DNA damage repair deficiency, and promising novel targeted- and immunotherapies regimens, such as PSMA-radioligand therapy, PARP inhibition and PD-1/PD-L1 and CTLA‑4 checkpoint therapy. We anticipate that these agents in monotherapy and in combination regimens will alter uro-oncological patient management within the next ten years.

scholarly journals Local and systemic morbidities of de novo metastatic prostate cancer in Singapore: insight from 685 consecutive patients from a large prospective Uro-oncology registry

BMJ Open ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. e034331 ◽  
Author(s):  
Yu Guang Tan ◽  
Leonard Pang ◽  
Farhan Khalid ◽  
Randy Poon ◽  
Hong Hong Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Metastatic Prostate Cancer ◽  
Group Performance ◽  
De Novo ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
High Volume ◽  
Secondary Outcome ◽  
Systemic Complications

ObjectiveTo evaluate the incidence and management of local and systemic complications afflicting patients with de novo metastatic prostate cancer (mPCa) in Singapore.DesignRetrospective analysis of a large prospective Uro-oncology registry of mPCa.SettingThis study is carried out in a tertiary hospital in Singapore.ParticipantsWe reviewed our institution’s prospectively maintained database of 685 patients with mPCa over a 20-year period (1995–2014). Patients with non-mPCa or those progressed to metastatic disease after previous curative local treatments were excluded.Primary and secondary outcome measuresThe primary outcome was to evaluate the systemic and local morbidity rates associated with mPCa. Local complication was defined as the need for palliative procedures to relieve urinary obstruction, worsening renal function or refractory haematuria, while systemic complication was related to radiographic evidence of skeletal-related pathological fractures. Secondary outcomes analysed were the management and overall survival patterns over 20 years.Results237 (34.6%) patients required local palliative treatments. 88 (12.8%) patients presented with acute urinary retention, 23 patients (9.7%) required repetitive local palliative treatments. On multivariate analyses, prostate-specific antigen >100 (p=0.02) and prostate volume >50 g (p=0.03) were independent prognostic factors for significant obstruction requiring palliative procedures. 118 (17.2%) patients developed skeletal fractures, with poor Eastern Cooperative Oncology Group Performance (ECOG) status (p=0.01) and high volume bone metastasis (p<0.01) independently predictive of skeletal fractures. Altogether, 653 (95.3%) patients received androgen deprivation therapy (ADT), with the median time to castrate resistance of 21.4 months (IQR 7–27). The median overall survival was 45 months (IQR 20–63), with prostate cancer mortality of 81.4%. Improved overall survival was observed from 41.6 months (1995–1999) to 47.8 months (2010–2014) (p<0.01).ConclusionMorbidities and complications arising from mPCa are more common and debilitating than we thought, often requiring immediate palliative treatments, while many necessitate repeated interventions with progression.

scholarly journals Genomic Profiles of De Novo High- and Low-Volume Metastatic Prostate Cancer: Results From a 2-Stage Feasibility and Prevalence Study in the STAMPEDE Trial

2020 ◽  
pp. 882-897 ◽  
Author(s):  
Clare Gilson ◽  
Fiona Ingleby ◽  
Duncan C. Gilbert ◽  
Marina A. Parry ◽  
Nafisah B. Atako ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Chromatin Remodeling ◽  
Metastatic Prostate Cancer ◽  
De Novo ◽  
High Volume ◽  
Pi3k Pathway ◽  
Mismatch Repair Gene ◽  
Copy Number Loss ◽  
Hormone Sensitive ◽  
Low Volume

PURPOSE The STAMPEDE trial recruits men with newly diagnosed, high-risk, hormone-sensitive prostate cancer. To ascertain the feasibility of targeted next-generation sequencing (tNGS) and the prevalence of baseline genomic aberrations, we sequenced tumor and germline DNA from patients with metastatic prostate cancer (mPCa) starting long-term androgen-deprivation therapy (ADT). METHODS In a 2-stage approach, archival, formalin-fixed, paraffin-embedded (FFPE) prostate tumor core biopsy samples were retrospectively subjected to 2 tNGS assays. Prospective enrollment enabled validation using tNGS in tumor and germline DNA. RESULTS In stage 1, tNGS data were obtained from 185 tumors from 287 patients (65%); 98% had de novo mPCa. We observed PI3K pathway aberrations in 43%, due to PTEN copy-number loss (34%) and/or activating mutations in PIK3 genes or AKT (18%) and TP53 mutation or loss in 33%. No androgen receptor ( AR) aberrations were detected; RB1 loss was observed in < 1%. In stage 2, 93 (92%) of 101 FFPE tumors (biopsy obtained within 8 months) were successfully sequenced prospectively. The prevalence of DNA damage repair (DDR) deficiency was 14% (somatic) and 5% (germline). BRCA2 mutations and mismatch repair gene mutations were exclusive to high-volume disease. Aberrant DDR (22% v 15%), Wnt pathway (16% v 4%), and chromatin remodeling (16% v 8%) were all more common in high-volume compared with low-volume disease, but the small numbers limited statistical comparisons. CONCLUSION Prospective genomic characterization is feasible using residual diagnostic tumor samples and reveals that the genomic landscapes of de novo high-volume mPCa and advanced metastatic prostate cancer have notable similarities (PI3K pathway, DDR, Wnt, chromatin remodeling) and differences ( AR, RB1). These results will inform the design and conduct of biomarker-directed trials in men with metastatic hormone-sensitive prostate cancer.

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