Luminal B subtype as a predictive biomarker of docetaxel benefit for newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC): A correlative study of E3805 CHAARTED.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 162-162 ◽  
Author(s):  
Anis Hamid ◽  
Xin Victoria Wang ◽  
Yu-Hui Chen ◽  
Felix Y Feng ◽  
Robert Benjamin Den ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
De Novo ◽  
Local Therapy ◽  
Microarray Platform ◽  
High Volume ◽  
Predictive Biomarker ◽  
Luminal A ◽  
Luminal B ◽  
Basal Subtype

162 Background: Through gene expression profiling (GEP), the PAM50 classifier demonstrates prognostic value in localized prostate cancer (PCa). Pre-clinical drug response models predict increased taxane sensitivity in luminal subtypes compared to basal subtype. Men with mHSPC and high-risk features have greatest benefit from androgen deprivation therapy (ADT) plus docetaxel (D) vs ADT alone. We therefore sought to test the prognostic and predictive value of PAM50 in pre-ADT specimens from E3805 CHAARTED. Methods: Whole transcriptomic profiling of formalin-fixed, paraffin-embedded primary PCa biopsies from pts enrolled in the E3805 CHAARTED trial of ADT vs ADT+D was performed using the Human Exon 1.0 ST microarray platform (Decipher Biosciences). Normalized gene expression was used to classify subjects as luminal A, luminal B or basal subtype. Multivariable analyses (MVA) adjusted for ECOG status, de novo metastasis vs prior local therapy and volume of disease. The primary endpoint was overall survival (OS). Secondary endpoint was time to castration resistant PCa (TTCRPC). Results: Successful GEP was completed in 160 of 198 pts with available specimens. Eighty (50%), 77 (48%) and 3 (2%) pts were classified as luminal B, basal and luminal A, respectively. High volume disease was similarly present in luminal B (79%) and basal (78%) subtypes. In the ADT arm, luminal B subtype was associated with shorter OS vs basal (HR 1.75, p=0.05); consistent in MVA. Pts with luminal B subtype treated with ADT+D showed significant improvement in TTCRPC and OS (Table). By contrast, basal subtype showed no OS benefit from ADT+D even in pts with high volume disease. Conclusions: We demonstrate that GEP identifies tumor subtypes associated with differential benefit from chemohormonal therapy for mHSPC. Luminal B subtype is associated with poorer OS with ADT alone and benefits from addition of D. Basal subtype shows a lack of OS benefit from upfront ADT+D. We plan to validate these findings in independent trial cohorts.[Table: see text]

Luminal and basal subtyping of prostate cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 3-3 ◽  
Author(s):  
Felix Yi-Chung Feng ◽  
Shuang Zhao ◽  
Seiwon Laura Chang ◽  
Nicholas Erho ◽  
Jonathan Lehrer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Cancer Biology ◽  
Microarray Platform ◽  
Luminal A ◽  
Cancer Specific Survival ◽  
Free Survival ◽  
Luminal B ◽  
Clinical Tools ◽  
Prostate Cancers

3 Background: There is a clear need to develop a clinically relevant molecular subtyping approach for prostate cancer. We hypothesized that prostate cancer can be subtyped based on luminal versus basal lineage. Methods: We applied the PAM50 classifier, which is used clinically to identify luminal and basal cancers in breast cancer, to subtype a total of 3,782 prostate cancer samples using a high-density microarray platform run in a CLIA-certified laboratory. We examined the associations of these subtypes and clinical outcomes. Results: We demonstrate that PAM50 segregates prostate cancer into three reproducible subtypes in both retrospective cohorts and on prospective validation: luminal A (33.3%-34.3%), luminal B (28.5%-32.6%), and basal (34.1%-37.1%). Luminal B prostate cancers exhibited the worst clinical prognoses, followed by basal and luminal A subtypes (10-year biochemical recurrence-free survival: 29/39/41%; distant metastasis-free survival: 53/73/73%; prostate cancer-specific survival: 78/86/89%; overall survival: 69/80/82% respectively) on both univariable and multivariable analyses accounting for standard clinicopathologic prognostic factors. Known luminal lineage markers, such as NKX3.1 and KRT18, and the basal lineage CD49f signature, were enriched in luminal- and basal-like cancers respectively, demonstrating the connection between these subtypes and established prostate cancer biology. While both luminal-like subtypes were associated with increased AR expression and signaling, only luminal B prostate cancers were significantly associated with post-operative response to androgen deprivation therapy (ADT) in a subset analysis matching patients based on clinicopathologic variables (interaction p = 0.006, luminal B 10-year metastasis: 33% (treated) vs. 55% (untreated), non-luminal B: 37% (treated) vs. 21% (untreated)). Conclusions: These findings contribute novel insight into the biology of prostate cancer, and provide translatable clinical tools for personalizing post-operative ADT for patients with prostate cancer. Similar to breast cancer, these findings suggest that luminal/basal subtyping may be useful in treatment selection in prostate cancer.

Luminal and basal subtyping of metastatic castration-resistant prostate cancer (mCRPC) and its clinical implications.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 197-197 ◽  
Author(s):  
Won Kim ◽  
Eric Jay Small ◽  
Rahul Raj Aggarwal ◽  
Robert Benjamin Den ◽  
Jonathan Lehrer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Drug Response ◽  
Metastatic Tumor ◽  
Localized Prostate Cancer ◽  
Patient Specific ◽  
Expression Data ◽  
Castration Resistant Prostate Cancer ◽  
Luminal A ◽  
Luminal B

197 Background: The PAM50 gene expression classifier (PAM50) identifies luminal and basal subtypes and predicts response to androgen deprivation therapy in localized prostate cancer. The clinical utility of using PAM50 to molecularly subtype mCRPC was evaluated. Methods: PAM50 was applied to RNA expression data from 86 metastatic tumor biopsies from the SU2C-AACR-PCF West Coast Prostate Cancer Dream Team (WCDT; NCT02432001). Overall survival (OS) differences between luminal A (LuA), luminal B (LuB), or basal patients (pts) were determined using Kaplan-Meier analyses. PAM50 was also applied to 15,136 prospectively collected radical prostatectomy (RP) samples from the Decipher GRiD database (NCT02609269). Drug response signatures (DRS) for 89 drugs were derived using publicly available data from the NCI60 cell line panel, and applied to gene expression data from the RP samples to predict patient-specific drug sensitivities. Differences in DRS as a function of PAM50 subtype were assessed using the Pearson’s chi-squared test. Results: The application of PAM50 to mCRPC transcriptional data segregated pts into LuA, LuB, and basal populations (43%, 14%, and 43%, respectively). The median OS for LuA, LuB, and basal pts was 20.6 months, 9.5 months, and 10.4 months, respectively (p=0.04), which was consistent with localized prostate cancer where LuB pts have the worst prognosis. DRS analyses revealed statistically significant differences in drug sensitivities, with LuA and LuB pts predicted to be markedly more sensitive to docetaxel than basal pts (p<0.00001), and basal pts predicted to be markedly more sensitive to platinums and etoposide than LuA and LuB pts (p<0.00001). Conclusions: PAM50 subtyping is prognostic in mCRPC, with LuA pts demonstrating the longest OS. Luminal and basal subtypes have distinct in silico drug response profiles that may be associated with response to mCRPC therapies. Prospective testing of DRS as a biomarker to guide treatment in mCRPC is warranted. Clinical trial information: NCT02432001, NCT02609269.

Multi-institutional evaluation of the clinical outcomes and genomic correlates of African Americans with metastatic castration-sensitive prostate cancer (mCSPC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 17-17
Author(s):  
Meredith MI Freeman ◽  
Ellen Jaeger ◽  
Jason Zhu ◽  
Audrey Phone ◽  
Roberto Nussenzveig ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Retrospective Analysis ◽  
Clinical Outcomes ◽  
De Novo ◽  
High Volume ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Treatment Intensification ◽  
Radium 223 ◽  
Incidence And Mortality

17 Background: Prostate cancer incidence and mortality is higher in African American (AA) as compared with non-AA men. The outcomes of mCSPC have significantly improved through treatment intensification yet, AA representation in those studies was suboptimal. We aimed to report the clinical, treatment outcomes and genomic data of AA men with mCSPC. Methods: Retrospective analysis of consecutive AA men with mCSPC at six Academic Institutions. The primary objective was to report the baseline characteristics and treatment patterns of mCSPC AA patients. The secondary objectives included the germline and somatic data and the clinical outcomes including PSA response, progression-free survival and subsequent treatments. Results: A total of 71 patients, median age 63 years (range, 41-84) with 58% Gleason 8-10, initial PSA of 69.8 ng/mL (0.02-7650), 59% with de-novo and 55% with high-volume (CHAARTED criteria; 20% visceral) disease, were included in this analysis. Twenty-two patients (31%) were treated with androgen deprivation therapy (ADT; 67% prior to year 2017), while 24%, 45% and 3% received docetaxel (median 6 cycles), abiraterone acetate and enzalutamide, respectively. Two patients received triplet therapy with ADT/docetaxel plus abiraterone or enzalutamide. Undetectable PSA was achieved in 35% after a median of 8.9 months (1.8-22.3). Among patients with mCSPC who received radiation therapy to prostate (n = 8), 89% had low volume disease. At time of cut off, thirty-two patients developed CRPC and the estimated median time to CRPC was 2.9 years (95% CI, 1.6-4.2). Subsequent therapies (n = 29) included abiraterone acetate (41%), enzalutamide (24%), bicalutamide (10%), radium-223 (7%), chemotherapy (7%), sipuleucel-T (3%) and others (7%). Five patients (8%) had pathogenic germline alterations (n = 2 BRCA1; n = 1 HOXB13, PALB2 and PMS2). Additionally, the most common somatic alterations among tested patients (n = 27) included CDK12, SPOP, TMPRSS2-ERG fusion, and TP53, all in 11% frequency. Of note, n = 2 BRCA1 and n = 1 high MSI/TMB. Conclusions: In one of the largest reported cohorts to our knowledge, mCSPC AA presented with a high number of de-novo and high-volume disease and might harbor a different germline and somatic genomic profile. The outcomes were comparable to contemporary phase III trials with treatment intensification, yet 31% were treated with ADT. Despite the known limitations associated with retrospective analysis, these data support prior observations where AA might have better initial PSA responses to ADT-based strategies compared with Caucasians, requiring further validation.

scholarly journals Analysis of the Gene Expression Profile of Stromal Pro-Tumor Factors in Cancer-Associated Fibroblasts from Luminal Breast Carcinomas

Diagnostics ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 865 ◽  
Author(s):  
Noemi Eiro ◽  
Sandra Cid ◽  
María Fraile ◽  
Jorge Ruben Cabrera ◽  
Luis O. Gonzalez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Cancer Associated Fibroblasts ◽  
Breast Carcinomas ◽  
Luminal A ◽  
Luminal B

Luminal tumors are the most frequent type of breast carcinomas showing less tumor aggressiveness, although heterogeneity exists in their clinical outcomes. Cancer-associated fibroblasts (CAFs) are a key component of the tumor stroma which contribute to tumor progression. We investigated by real-time PCR the gene expression of 19 factors implicated in tumor progression. Those factors included the calcium-binding protein S100A4, several growth factors (FGF2, FGF7, HGF, PDGFA, PDGFB, TGFβ, VEGFA, and IGF2), and we also studied inflammatory cytokines (IL6 and IL8), chemokines (CCL2, CXCL12), important proteases (uPA, MMP2, MMP9 and MMP11), the nuclear factor NFκB, and the metalloprotease inhibitor TIMP1, from luminal A and luminal B breast carcinoma CAFs. We performed a similar analysis after co-culturing CAFs with MCF-7 and MDA-MB-231 breast cancer cell lines. MMP-9 and CCL2 gene expressions were higher in CAFs from luminal B tumors. We also found different patterns in the induction of pro-tumoral factors from different CAFs populations co-cultured with different cancer cell lines. Globally, CAFs from luminal B tumors showed a higher expression of pro-tumor factors compared to CAFs from luminal A tumors when co-cultured with breast cancer cell lines. Moreover, we found that CAFs from metastatic tumors had higher IGF-2 gene expression, and we detected the same after co-culture with cell lines. Our results show the variability in the capacities of CAFs from luminal breast carcinomas, which may contribute to a better biological and clinical characterization of these cancer subtypes.

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.

Epigenetic aspects of triple-negative in patients with breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1041-1041
Author(s):  
Joaquina Martínez-Galan ◽  
Sandra Rios ◽  
Juan Ramon Delgado ◽  
Blanca Torres-Torres ◽  
Jesus Lopez-Peñalver ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Dna Methylation ◽  
Triple Negative ◽  
Breast Cancer Subtype ◽  
Regulation Of Gene Expression ◽  
Breast Cancer Subtypes ◽  
Luminal A ◽  
Cancer Subtypes ◽  
Luminal B

1041 Background: Identification of gene expression-based breast cancer subtypes is considered a critical means of prognostication. Genetic mutations along with epigenetic alterations contribute to gene-expression changes occurring in breast cancer. However, the reproducibility of differential DNA methylation discoveries for cancer and the relationship between DNA methylation and aberrant gene expression have not been systematically analysed. The present study was undertaken to dissect the breast cancer methylome and to deliver specific epigenotypes associated with particular breast cancer subtypes. Methods: By using Real Time QMSPCR SYBR green we analyzed DNA methylation in regulatory regions of 107 pts with breast cancer and analyzed association with prognostics factor in triple negative breast cancer and methylation promoter ESR1, APC, E-Cadherin, Rar B and 14-3-3 sigma. Results: We identified novel subtype-specific epigenotypes that clearly demonstrate the differences in the methylation profiles of basal-like and human epidermal growth factor 2 (HER2)-overexpressing tumors. Of the cases, 37pts (40%) were Luminal A (LA), 32pts (33%) Luminal B (LB), 14pts (15%) Triple-negative (TN), and 9pts (10%) HER2+. DNA hypermethylation was highly inversely correlated with the down-regulation of gene expression. Methylation of this panel of promoter was found more frequently in triple negative and HER2 phenotype. ESR1 was preferably associated with TN(80%) and HER2+(60%) subtype. With a median follow up of 6 years, we found worse overall survival (OS) with more frequent ESR1 methylation gene(p>0.05), Luminal A;ESR1 Methylation OS at 5 years 81% vs 93% when was ESR1 Unmethylation. Luminal B;ESR1 Methylation 86% SG at 5 years vs 92% in Unmethylation ESR1. Triple negative;ESR1 Methylation SG at 5 years 75% vs 80% in unmethylation ESR1. HER2;ESR1 Methylation SG at 5 years was 66.7% vs 75% in unmethylation ESR1. Conclusions: Our results provide evidence that well-defined DNA methylation profiles enable breast cancer subtype prediction and support the utilization of this biomarker for prognostication and therapeutic stratification of patients with breast cancer.

Burden of metastatic hormone-sensitive prostate cancer to identify men more likely to benefit from early docetaxel.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 136-136 ◽  
Author(s):  
Gwenaelle Gravis ◽  
Jean-Marie Boher ◽  
Yu-Hui Chen ◽  
Glenn Liu ◽  
Karim Fizazi ◽  
...  
Keyword(s):  
Overall Survival ◽  
De Novo ◽  
Local Treatment ◽  
Local Therapy ◽  
High Volume ◽  
Curative Intent ◽  
Consistent Effect ◽  
Visceral Metastases ◽  
Definition Of

136 Background: Patients with a low burden of metastatic disease and who relapse after localized therapy with curative intent have a longer overall survival. It is unclear whether these patients benefit from early docetaxel (D). Methods: Patients in GETUG-AFU15 (N = 385, median follow-up 84 mo) and CHAARTED (N = 790, median follow up 54 mo) were randomized to ADT alone or ADT + D and outcomes described using the same definition of high volume (HV) and low volume (LV) disease. (HV: visceral metastases and/or 4 or more bone metastases with at least one outside the axis) and whether the patients had prior local therapy or not. Results: Table 1 details across both studies that de novo HV group treated with ADT alone has the shortest overall survival and D has a consistent effect in improving OS. In contrast, in both studies patients with LV disease had a much longer OS with no evidence that D improved OS. Conclusions: There was no apparent survival benefit in CHAARTED and GETUG-15 studies with D for LV whether patients had prior local treatment or not. Across both studies, early D had a consistent effect and improved OS in HV pts especially those with no prior local therapy. Partial Support and drug supply by Sanofi. Clinical trial information: NCT00104715, NCT00309985. [Table: see text]

Real-world experience with docetaxel for castration-sensitive prostate cancer from a population-based analysis.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 297-297 ◽  
Author(s):  
Jean-Michel Lavoie ◽  
Kevin Zou ◽  
Daniel Khalaf ◽  
Bernhard J. Eigl ◽  
Christian K. Kollmannsberger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
De Novo ◽  
Performance Status ◽  
Clinical Effectiveness ◽  
High Volume ◽  
Population Based ◽  
Phase Iii ◽  
Phase Iii Clinical Trials ◽  
Cancer Agency ◽  
Grade 3

297 Background: Phase III clinical trials have demonstrated efficacy with an overall survival (OS) benefit for the addition of docetaxel (DOC) to androgen deprivation therapy (ADT) for the treatment of metastatic castration-sensitive prostate cancer (mCSPC). The clinical effectiveness of DOC with ADT in the general patient population remains undefined. Methods: A population-based retrospective review was conducted of patients (pts) with mCSPC who received DOC at the BC Cancer Agency from 04/2015 to 02/2017. Patient and disease characteristics were extracted. Safety and clinical-effectiveness were evaluated. Results: 183 records were identified; 156 pts received DOC in the mCSPC setting. Baseline characteristics included a median age of 67 years (range 44-86) and visceral metastases (mets) present in 18%; 80% had high volume disease with 74% having > 3, and 54% > 10 bone mets; 76% had de-novo metastatic disease. All 6 planned DOC cycles were delivered in 126 cases (81%); it was stopped early for: toxicity in 15 (10%), unrelated death in 1 (0.6%), pt preference in 5 (3%) or disease progression in 9 (6%) cases. Dose reductions and delays were required in 61 (39%) and 25 (16%) cases, respectively. Grade 3-5 adverse events were noted in 62 (40%) cases, with 28 (18%) cases of febrile neutropenia (FN); there were no treatment-related deaths. Pts with FN had more bone mets (p = 0.046), but there was no difference in time from start of ADT to initiation of docetaxel, age, baseline performance status, PSA, or visceral involvement. PSA ≤ 0.2 ng/L was achieved in 41 (28%) cases after 6 months of ADT and maintained in 13 (8%) cases after 12 months. 41% of pts had developed CRPC within 1-yr, with a median time to CRPC of 14.3 months. Treatment for CRPC was given in 54 cases, with most pts receiving either abiraterone or enzalutamide (87%) with a PSA decline ≥50% occurring in 47%. Conclusions: Effectiveness of DOC with ADT in a general population of pts with mCSPC was associated with poorer outcomes and high rates of toxicity compared to the phase III studies. Response rates to first-line treatment for mCRPC with abiraterone or enzalutamide appear similar to those previously reported.

Why Chemotherapy Should be Given Early for Men with Metastatic Prostate Cancer

2015 ◽  
pp. e263-e269 ◽  
Author(s):  
Leonel F. Hernandez-Aya ◽  
Maha Hussain
Keyword(s):  
Prostate Cancer ◽  
De Novo ◽  
High Volume ◽  
High Response Rate ◽  
Phase Iii ◽  
Incurable Disease ◽  
Castration Resistant ◽  
Castrate Resistant Prostate Cancer ◽  
Hormone Sensitive ◽  
Castrate Resistant

Metastatic hormone-sensitive prostate cancer (mHSPC) is an incurable disease, and despite a high response rate to androgen-deprivation therapy (ADT), outcomes have not significantly changed for many decades. Earlier attempts at multitargeted strategies with the addition of cytotoxic chemotherapy to ADT did not affect survival. As more effective therapies are emerging, including cytotoxic therapy for patients with metastatic castrate-resistant prostate cancer (mCRPC), there is increasing interest for testing these drugs earlier in the disease course. The premise is that agents with clinical benefit in advanced mCRPC may have a better effect if used preemptively before the development of significant resistance and to attack earlier de novo androgen resistant/independent clones. The recent results of the phase III clinical trial E3805 investigating ADT with or without docetaxel in mHSPC provide compelling support for this strategy. Docetaxel combined with ADT significantly improved overall survival from 44 to 57.6 months (p = 0.0003), particularly in patients with high-volume disease (from 32.2 to 49.2 months; p = 0.0006). Longer follow-up is needed to assess the effect on patients with low disease burden. Further studies are needed to further maximize the antitumor effect in patients with mHSPC and to investigate the effects of advancing therapy to this disease setting on the efficacy of respective agents in the castration-resistant setting.

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