scholarly journals Genomic profiles and clinical outcomes in primary versus secondary metastatic hormone‐sensitive prostate cancer

The Prostate ◽  
2021 ◽  
Author(s):  
Emily Nizialek ◽  
Su Jin Lim ◽  
Hao Wang ◽  
Pedro Isaacsson Velho ◽  
Srinivasan Yegnasubramanian ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcomes ◽  
Hormone Sensitive

Association of basophil to lymphocyte ratio (BLR) with clinical outcomes in metastatic hormone sensitive prostate cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17049-e17049
Author(s):  
Katherine Emilie Rhoades Smith ◽  
Limeng Wan ◽  
Yuan Liu ◽  
Jacqueline T Brown ◽  
Greta Russler ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcomes ◽  
Laboratory Data ◽  
Progression Free Survival ◽  
Continuous Variable ◽  
Cancer Center ◽  
Lymphocyte Ratio ◽  
Potential Biomarker ◽  
Significant Difference ◽  
Hormone Sensitive

e17049 Background: There is limited biomarker data available for metastatic hormone sensitive prostate cancer (mHSPC). Inflammatory markers found on routine clinical lab data, including leukocyte to lymphocyte ratios calculated from complete blood counts (CBC), is associated with clinical outcomes (CO) in different malignancies. We investigated the association between basophil-to-lymphocyte ratio (BLR) and CO in a racially diverse patient population with mHSPC. Methods: We performed a retrospective multicenter review from Winship Cancer Institute at Emory University and Georgia Cancer Center for Excellence at Grady Memorial Hospital (2014 – 2020). Demographics, disease characteristics, and laboratory data were collected at the start of upfront therapy with either docetaxel (DOC) or abiraterone (ABI). Overall survival (OS) and progression-free survival (PFS) were used to measure CO. Results: Included were 165 patients with mHSPC with a median follow-up time of 22.6 months. 89 (53.9%) were Black and 76 (46.1%) were Non-Black (White, Asian, or Hispanic). 106 (63%) had Gleason scores of 8-10 and 105 (63.6%) were classified as high-volume disease (per CHAARTED trial criteria). 92 (55.8%) received DOC and 73 (44.2%) received ABI. Worse CO were associated with high BLR at an optimal cut of 0.0265 (range 0 – 0.81 , mean of 0.03, standard deviation 0.09). Elevated BLR is associated with decreased OS (HR 3.51, 1.79 – 6.91, p <0.001) and PFS (HR 1.85, 1.14 – 3.00, p 0.013) in multivariable analyses (MVA). High BLR and low BLR groups were similar except for age as a continuous variable, which was associated with high BLR. Otherwise, there were no significant difference for all reported clinical characteristics, including drug (DOC vs ABI), race (Black vs Non-Black), Gleason, disease volume (per CHARRTED criteria), ECOG, or BMI. Conclusions: In mHSPC, high baseline BLR is associated with worse OS and PFS. Our results are the first to identify that BLR is associated with CO in mHSPC. Further study is needed to validate BLR as a potential biomarker.[Table: see text]

scholarly journals Clinical Outcomes and Racial Disparities in Metastatic Hormone‐Sensitive Prostate Cancer in the Era of Novel Treatment Options

2021 ◽  
Author(s):  
KatherineEmilie Rhoades Smith ◽  
Jacqueline Theresa Brown ◽  
Limeng Wan ◽  
Yuan Liu ◽  
Greta Russler ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Racial Disparities ◽  
Clinical Outcomes ◽  
Treatment Options ◽  
Novel Treatment ◽  
Hormone Sensitive

A pilot trial of neoantigen DNA vaccine in combination with nivolumab/ipilimumab and prostvac in metastatic hormone-sensitive prostate cancer (mHSPC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. TPS192-TPS192
Author(s):  
Dhruv Bansal ◽  
Rachel Beck ◽  
Vivek Arora ◽  
Eric Marshall Knoche ◽  
Joel Picus ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Immune Responses ◽  
Clinical Outcomes ◽  
Dna Vaccine ◽  
Single Agent ◽  
Phase Iii ◽  
Free Survival ◽  
Hormone Sensitive ◽  
Docetaxel Chemotherapy

TPS192 Background: Despite robust advances in the use of immune checkpoint blockade (ICB) across multiple cancer types, responses in prostate cancer remain suboptimal. Overall response rates for single-agent ICB in prostate cancer are low, but recent modest gains have been made with ipilimumab and nivolumab combination therapy in metastatic castrate-resistant prostate cancer. Prostvac-VF Tricom is a therapeutic vaccine that incorporates DNA for the shared self-antigen PSA into the vaccinia (or fowlpox) virus strain. A large randomized phase III clinical trial recently showed no improvement in overall survival (OS) with Prostvac compared with placebo, suggesting that a combinatorial approach is warranted. Personalized neoantigen vaccines based on specific mutated epitopes may have the ability to overcome immunoresistance seen with self antigens. Even in low mutational burden tumors like prostate cancer, T cell responses against neoantigens are observed in patients with favorable clinical outcomes, supporting neoantigen vaccination as a promising therapeutic strategy. Improvements in computational genomics and predictive algorithms have allowed the incorporation of MHC class II neoepitopes and those from gene fusion events relevant in prostate cancer. We thus hypothesized that a strategy utilizing both shared antigen (Prostvac) and personalized MHC-I and MHC-II neoantigen vaccines combined with dual ICB would induce robust immune responses and improve clinical outcomes. To maximize tumor burden reduction and minimize tumor-mediated immunoresistence, we are evaluating this novel strategy in patients with metastatic hormone-sensitive prostate cancer (mHSPC) who have completed frontline docetaxel chemotherapy. Methods: This ongoing trial (NCT03532217) began accrual in September 2018. Eighteen of 20 planned patients have been enrolled to date. Eligible patients have histologically confirmed high risk/volume mHSPC defined as 4 or more sites of metastatic disease or visceral involvement. Patients receive continuous androgen deprivation therapy (ADT) and have completed upfront docetaxel chemotherapy. Patients begin treatment with Prostvac-VF in combination with ipilimumab (1 mg/kg every 3 weeks for 2 doses), and nivolumab (3 mg/kg every 3 weeks for 6 doses) within 60 days of the last dose of docetaxel. Subsequently, patients receive nivolumab 480 mg IV every 4 weeks in conjunction with a personalized neoantigen DNA vaccine administered monthly via intramuscular electroporation. The primary objective of this exploratory study is to assess the feasibility, safety/tolerability, and immune responses of this combination strategy. Key secondary objectives include failure-free survival and milestone survival at 2 years, PSA response, and radiographic progression-free survival. Clinical trial information: NCT03532217.

AR Copy Number and AR Signaling-directed Therapies in Castrationresistant Prostate Cancer

2018 ◽  
Vol 18 (9) ◽  
pp. 869-876
Author(s):  
Samanta Salvi ◽  
Vincenza Conteduca ◽  
Cristian Lolli ◽  
Sara Testoni ◽  
Valentina Casadio ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Copy Number ◽  
Clinical Trial Design ◽  
Complete Information ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Anti Cancer ◽  
Hormone Sensitive ◽  
Predictive And Prognostic Biomarker

Background: Adaptive upregulation of Androgen Receptor (AR) is the most common event involved in the progression from hormone sensitive to Castration-Resistant Prostate Cancer (CRPC). AR signaling remains the main target of new AR signalling-directed therapies such as abiraterone and enzalutamide in CRPC patients. Objective: In this review, we discuss general mechanisms of resistance to AR-targeted therapies, with a focus on the role of AR Copy Number (CN). We reported methods and clinical applications of AR CN evaluation in tissue and liquid biopsy, thus to have a complete information regarding its role as predictive and prognostic biomarker. Conclusion: Outcomes of CRPC patients are reported to be highly variable as the consequence of tumor heterogeneity. AR CN could contribute to patient selection and tumor monitoring in CRPC treated with new anti-cancer treatment as abiraterone and enzalutamide. Further studies to investigate AR CN effect to these agents and its potential combination with other prognostic or predictive clinical factors are necessary in the context of harmonized clinical trial design.

Sign in / Sign up

Export Citation Format

Share Document