scholarly journals Metastatic castration resistant prostate cancer with squamous cell, small cell, and sarcomatoid elements—a clinicopathologic and genomic sequencing-based discussion

2019 ◽  
Vol 36 (3) ◽  
Author(s):  
Steven C. Weindorf ◽  
Alexander S. Taylor ◽  
Chandan Kumar-Sinha ◽  
Dan Robinson ◽  
Yi-Mi Wu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Squamous Cell ◽  
Small Cell ◽  
Genomic Sequencing ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

Genomic predictors of benefit of docetaxel (D) and next-generation hormonal therapy (NHT) in metastatic castration resistant prostate cancer (mCRPC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5018-5018
Author(s):  
Anis Hamid ◽  
Himisha Beltran ◽  
Atish Dipankar Choudhury ◽  
Christopher Sweeney
Keyword(s):  
Prostate Cancer ◽  
Therapeutic Strategy ◽  
Median Overall Survival ◽  
Radiographic Progression ◽  
Small Cell ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Time To Treatment Failure

5018 Background: Predictive genomic biomarkers in mCRPC remain elusive. Prior studies suggest that tumor suppressor (TS) loss is prognostic, and may result in less benefit from NHT, but no impact on D efficacy. We assessed genomic predictors of differential benefit of androgen receptor-targeted therapy and chemotherapy for mCRPC. Methods: Patients with mCRPC and targeted exome sequencing of biopsies obtained after metastatic diagnosis were identified (n=109). Patients with pure small cell histology (n=6) were excluded. Time from NHT or D start to clinical/radiographic progression (time to treatment failure, TTTF) was estimated by Kaplan-Meier method, with censoring at next therapy or last follow-up for non-progressors. Results: 80.1% of patients had bone and/or lymph node-only metastases at mCRPC diagnosis. In total, 87/103 (84.5%) and 61/103 (59.2%) received NHT and D for mCRPC, respectively. Median overall survival was 4.5 years from first mCRPC. The frequency and predictive association of selected recurrently-altered genes are detailed in the table. PTEN alterations (alts) were associated with worse TTTF on NHT, but not D, and a similar trend was observed with BRCA2. Biallelic RB1 loss was strongly predictive, conferring significantly shorter TTTF on both NHT and D. A score based on presence of tumor PTEN alt (1) and/or biallelic RB1 alt (1) was predictive of TTTF on NHT (median TTTF of score 0 vs 1 vs 2: 14.7 vs 12 vs 3.8 months; log rank p=0.003). Conclusions: The presence of single or compound PTEN and RB1 alts predict poorer outcomes with NHT for mCRPC. Chemotherapy may be a preferred therapeutic strategy for this patient population. [Table: see text]

Dramatically Elevated Circulating Tumor Cell Numbers in a Patient With Small Cell Neuroendocrine Carcinoma of the Prostate

2010 ◽  
Vol 134 (1) ◽  
pp. 120-123
Author(s):  
Fanny Chan ◽  
Oscar Goodman ◽  
Louis Fink ◽  
Nicholas J. Vogelzang ◽  
David Pomerantz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Specific Antigen ◽  
Metastatic Breast ◽  
Circulating Tumor Cell ◽  
Small Cell ◽  
Castration Resistant Prostate Cancer ◽  
Normal Prostate ◽  
Castration Resistant

Abstract Detection of circulating tumor cells in whole blood is a useful prognostic tool for patients with castration-resistant prostate cancer, as well as for patients with metastatic breast cancer and colorectal carcinoma. In this report, we present the case of a patient with neuroendocrine small cell prostate cancer with normal prostate-specific antigen levels throughout the course of disease but who had markedly elevated circulating tumor cells, as detected with the CellSearch (Veridex) system.

Open-label, phase II study of ladiratuzumab vedotin (LV) for castration-resistant prostate cancer (SGNLVA-005, trial-in-progress).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. TPS185-TPS185
Author(s):  
Amna Falak Sher ◽  
Justine Yang Bruce ◽  
Nashat Y. Gabrail ◽  
Ian Churchill Anderson ◽  
Anna Patrikidou ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Response Rate ◽  
Small Cell ◽  
Advanced Solid Tumors ◽  
Castration Resistant Prostate Cancer ◽  
Small Cell Lung ◽  
Open Label ◽  
Safety And Efficacy ◽  
Castration Resistant ◽  
Open Label Phase

TPS185 Background: LIV-1 is a transmembrane protein expressed in a variety of cancer types. SGN-LIV1A, or ladiratuzumab vedotin (LV), is a novel investigational humanized IgG1 antibody-drug conjugate (ADC) directed against LIV-1. LV mediates delivery of monomethyl auristatin E (MMAE), which drives antitumor activity through cytotoxic cell killing and induces immunogenic cell death. In a phase 1 study, LV was tolerable and active in heavily pretreated patients with metastatic breast cancer (Modi 2017). This study is currently evaluating the safety and efficacy of LV in different advanced solid tumors with various LIV-1 expression, including metastatic castration-resistant prostate cancer (mCRPC), advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma, esophageal squamous cell carcinoma, small cell lung cancer (SCLC), non-small cell lung cancer (squamous and nonsquamous), head and neck squamous cell carcinoma, and melanoma. Methods: SGNLVA-005 (NCT04032704) is an open-label, phase 2 study evaluating LV monotherapy in patients with previously treated, locally advanced unresectable or metastatic advanced solid tumors, including mCRPC. Patients with mCRPC will receive LV administered as a 30 minute intravenous infusion (IV) at 1.25 mg/kg every 1 week. Up to 30 patients with mCRPC will be enrolled. Patients in the mCRPC cohort must have metastatic castration-resistant disease, have received no more than 1 prior line of androgen receptor-targeted therapy, have ≥28 days between androgen receptor-targeted therapy and start of study treatment, an Eastern Cooperative Oncology Group (ECOG) score of 0 or 1, and adequate organ function. In addition, mCRPC patients with measurable and non-measurable disease are eligible if the protocol-defined criteria are met. mCRPC patients must not have BRCA gene mutations, prior cytotoxic chemotherapy in the metastatic mCRPC setting, prior radioisotope therapy, or radiotherapy to ≥30% of bone marrow. Patients are not preselected based on tumor LIV-1 expression. Their tumor samples will be analyzed for correlation between LIV-1 expression and response. Safety and efficacy will be monitored throughout the study. Study objectives include objective tumor response rate per RECIST 1.1 and prostate-specific antigen (PSA) response rate per Prostate Cancer Clinical Trials Working Group 3 (both primary); safety and tolerability, disease control rate, duration of response, progression-free and overall survival, and pharmacokinetics and immunogenicity (all secondary); and pharmacodynamics. Study accrual is ongoing in the USA, Italy, South Korea, Taiwan, Australia, and the UK. Clinical trial information: NCT04032704.

ADRB2 expression in progressive metastatic castration-resistant prostate cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 145-145
Author(s):  
Daniel Kwon ◽  
Li Zhang ◽  
Adam Foye ◽  
William S. Chen ◽  
Felix Y Feng ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Performance Status ◽  
Multivariable Analysis ◽  
Neuroendocrine Differentiation ◽  
Small Cell ◽  
Rank Test ◽  
Rna Seq ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Ezh2 Expression

145 Background: The net oncogenic effect of the G protein-coupled receptor β2 adrenergic receptor ADRB2, which may induce neuroendocrine differentiation via cyclic AMP and protein kinase A and whose expression is epigenetically regulated by EZH2, is controversial. ADRB2 expression and associated clinical outcomes in metastatic castration-resistant prostate cancer (mCRPC) are unknown. Methods: This was a retrospective analysis of a cohort of men with mCRPC who were prospectively enrolled in the multi-center SU2C/PCF/AACR West Coast Prostate Cancer Dream Team study, in which biopsies of a metastatic site were obtained at disease progression. Specimens underwent laser capture microdissection and RNA-seq. ADRB2 expression was stratified by histology and transcriptional cluster based on prior unsupervised hierarchical transcriptome clustering, and correlated with EZH2 expression. ADRB2 expression (lowest quartile) was correlated with OS from time of biopsy by log rank test and a multivariable Cox proportional hazard model. Results: One-hundred and twenty-seven men with progressive mCRPC underwent metastatic biopsies and had sufficient tumor for RNA-seq. ADRB2 expression was lowest in the small cell-enriched transcriptional cluster (P<0.001), and correlated inversely with EZH2 expression (r=-0.28, P<0.01). Men with low ADRB2 expression had a shorter median OS than those with high (9.5 vs 18.9 mo, P=0.02). In multivariable analysis adjusting for small cell histology, performance status, LDH, and visceral metastases, high ADRB2 expression was associated with a trend towards longer OS (HR=0.65, 95% CI 0.41-1.02, P=0.06). Conclusions: Low ADRB2 expression is associated with worse OS in men with progressive mCRPC, and may be a means by which EZH2 confers resistance to antiandrogen therapy. Indirect ADRB2 stimulation with EZH2 inhibitors may improve outcomes. Validation in independent cohorts is necessary.

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