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.

Outcomes of older men receiving docetaxel for metastatic hormone-sensitive prostate cancer.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 82-82
Author(s):  
Daniel E Lage ◽  
M Dror Michaelson ◽  
Richard J. Lee ◽  
Joseph A. Greer ◽  
Jennifer S. Temel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Adverse Events ◽  
Older Men ◽  
Similar Proportion ◽  
Androgen Ablation ◽  
Younger Men ◽  
Hormone Sensitive ◽  
The Impact ◽  
Docetaxel Chemotherapy

82 Background: Most men who die of prostate cancer are older than 70 years, and the impact of therapy in this population is poorly defined. The ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) randomized men of all ages with metastatic hormone-sensitive prostate cancer (mHSPC) to receive androgen deprivation therapy (ADT) with or without docetaxel. Methods: The results of CHAARTED showed an overall survival (OS) benefit for the addition of docetaxel to ADT in men with mHSPC. In a secondary analysis of this trial, we assessed patient characteristics and OS in patients ≥70 years (“older men”) versus <70 years (“younger men”) with Cox proportional hazards models. Additionally, we compared adverse events, therapy completion rate, and subsequent treatment patterns between these two groups using Chi-squared tests. Results: Of the 790 patients enrolled, 177 (22.4%) were ≥70 years. A greater proportion of older men had an impaired performance status (Eastern Cooperative Oncology Group 1-2: 36.7% vs. 28.6%, p=0.038) and prior local therapy (31.7% vs. 25.9%, p<0.001) compared to younger men. Docetaxel + ADT resulted in improved OS in both older and younger men (Hazard Ratio [HR] 0.45, 95%CI: 0.25-0.80 for older men; HR 0.71, 95%CI: 0.53-0.95 for younger men). This treatment benefit was seen for subgroups of older men with high volume disease (HR 0.43, 95%CI 0.23-0.79) and de novo metastatic disease (HR 0.36, 95%CI 0.19-0.69). A similar proportion of older and younger men completed all six cycles of docetaxel (82.6% vs. 87.1%, p=0.28). Rates of grade 3-5 adverse events were similar between older and younger men (36.8% of older men vs. 26.8% of younger men, p=0.69). The rate of any Grade 4-5 adverse events did not differ significantly between older and younger men (14.9% vs. 11.9%, respectively, p=0.46). In the control arm, a smaller proportion of older men received subsequent cancer treatments (34.4% vs. 51.5%, p=0.017) or subsequent docetaxel (25.6% vs. 37.6%, p=0.035) compared to younger men. Conclusions: In summary, older men with mHSPC who were eligible to participate in a clinical trial had similar OS benefit and clinical outcomes compared to younger men when receiving docetaxel chemotherapy + ADT. Oncologists should consider docetaxel chemotherapy as a favorable treatment option for older men with mHSPC who are fit for chemotherapy. Clinical trial information: NCT00309985.

scholarly journals ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide or Placebo in Men With Metastatic Hormone-Sensitive Prostate Cancer

2019 ◽  
Vol 37 (32) ◽  
pp. 2974-2986 ◽  
Author(s):  
Andrew J. Armstrong ◽  
Russell Z. Szmulewitz ◽  
Daniel P. Petrylak ◽  
Jeffrey Holzbeierlein ◽  
Arnauld Villers ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiographic Progression ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Hormone Sensitive ◽  
Over Time

PURPOSE Enzalutamide, a potent androgen-receptor inhibitor, has demonstrated significant benefits in metastatic and nonmetastatic castration-resistant prostate cancer. We evaluated the efficacy and safety of enzalutamide in metastatic hormone-sensitive prostate cancer (mHSPC). METHODS ARCHES (ClinicalTrials.gov identifier: NCT02677896 ) is a multinational, double-blind, phase III trial, wherein 1,150 men with mHSPC were randomly assigned 1:1 to enzalutamide (160 mg/day) or placebo, plus androgen deprivation therapy (ADT), stratified by disease volume and prior docetaxel chemotherapy. The primary end point was radiographic progression-free survival. RESULTS As of October 14, 2018, the risk of radiographic progression or death was significantly reduced with enzalutamide plus ADT versus placebo plus ADT (hazard ratio, 0.39; 95% CI, 0.30 to 0.50; P < .001; median not reached v 19.0 months). Similar significant improvements in radiographic progression-free survival were reported in prespecified subgroups on the basis of disease volume and prior docetaxel therapy. Enzalutamide plus ADT significantly reduced the risk of prostate-specific antigen progression, initiation of new antineoplastic therapy, first symptomatic skeletal event, castration resistance, and reduced risk of pain progression. More men achieved an undetectable prostate-specific antigen level and/or an objective response with enzalutamide plus ADT ( P < .001). Patients in both treatment groups reported a high baseline level of quality of life, which was maintained over time. Grade 3 or greater adverse events were reported in 24.3% of patients who received enzalutamide plus ADT versus 25.6% of patients who received placebo plus ADT, with no unexpected adverse events. CONCLUSION Enzalutamide with ADT significantly reduced the risk of metastatic progression or death over time versus placebo plus ADT in men with mHSPC, including those with low-volume disease and/or prior docetaxel, with a safety analysis that seems consistent with the safety profile of enzalutamide in previous clinical trials in castration-resistant prostate cancer.

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

Retrospective cohort analysis of real-world clinical outcomes in nonmetastatic (M0) castration-resistant prostate cancer (CRPC) treated with novel androgen receptor pathway inhibitors (ARPI).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 51-51
Author(s):  
Richard Gagnon ◽  
Nimira S. Alimohamed ◽  
Alexander Watson ◽  
Eugene Batuyong ◽  
Alyssa Chow ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcomes ◽  
Real World ◽  
Retrospective Cohort ◽  
Cohort Analysis ◽  
Progression Free Survival ◽  
Rank Test ◽  
Castration Resistant Prostate Cancer ◽  
Survival Times ◽  
Free Survival

51 Background: The landscape of M0 CRPC has changed with the recent demonstration of metastasis-free survival (MFS) and overall survival (OS) improvements with the use of ARPIs in clinical trial settings. However, the extrapolation of this data to clinical practice is limited by strict exclusion criteria in these trials, including prior or concurrent malignancy, cardiovascular disease, or hypertension. The purpose of this study was to assess real-world outcomes in patients with M0 CRPC treated with ARPIs compared to historical controls. Methods: We designed a retrospective cohort study with the inclusion of patients in Alberta, Canada diagnosed with M0 CRPC between 2001-2020. Via chart review, we identified baseline characteristics, potential confounders, treatment details, and clinical outcomes. The primary outcome of interest was MFS. Secondary outcomes included: second progression-free survival (PFS2) and OS. Median survival times were measured using the Kaplan-Meier method and the log-rank test was used for comparison of outcomes based on ARPI exposure. Cox proportional hazard regression models were used to calculate hazard ratios (HR) accounting for impact of PSA doubling time (PSADT), use of osteoclast inhibiting agents, and presence of pelvic lymphadenopathy. Results: We identified 211 patients across multiple centres in Alberta with M0 CRPC, with 54 having received apalutamide (40/54), enzalutamide (7/54), or darolutamide (7/54). Median age at M0 CRPC diagnosis was 74 years; median PSADT was 4.4 months; and 19% of patients (40/211) had pelvic lymphadenopathy at diagnosis. Median MFS in patients treated with ARPIs was 47.5 months compared to 20.6 months in those not treated with ARPIs (HR, 0.23; 95% confidence interval [CI], 0.11-0.49; p < 0.001). Median PFS2 in ARPI treated patients was 66.3 months compared with 35.6 months (HR, 0.40; 95% CI, 0.18-0.87; p = 0.022). Median OS for patients treated with ARPI was not reached. Conclusions: Given the older age of men with advanced prostate cancer, real-world outcomes that include patients with comorbidities are important adjuncts to the interpretation of clinical trials exploring the benefit of novel therapeutics. Here, we demonstrate that in a real-world, unselected population of men with M0 CRPC, apalutamide, enzalutamide, and darolutamide seem to confer similar MFS and PFS2 benefits to those demonstrated in the SPARTAN, PROSPER, and ARAMIS studies. Real-world OS data remain immature and will be an important addition to these findings.

Cyto-KIK: A phase II trial of cytoreductive surgery in kidney cancer plus immunotherapy (nivolumab) and targeted kinase inhibition (cabozantinib).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS4598-TPS4598
Author(s):  
Karie Runcie ◽  
Eric A. Singer ◽  
Moshe Chaim Ornstein ◽  
Christopher B. Anderson ◽  
Matthew Dallos ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Phase Ii ◽  
Checkpoint Inhibitors ◽  
Recurrent Glioblastoma ◽  
Phase Iii ◽  
Cytoreductive Nephrectomy ◽  
Open Label ◽  
Orthotopic Mouse Model

TPS4598 Background: Despite recent therapeutic advancements in metastatic renal cell carcinoma (mRCC), only 5-10% of patients will achieve a complete response (CR) to therapy. Cytoreductive nephrectomy removes a large portion of the tumor which may be a source of immunosuppression driven by tumor cell-intrinsic factors in the tumor microenvironment. A pre-clinical orthotopic mouse model of aggressive metastatic triple negative breast cancer showed that neoadjuvant anti-PD-1 checkpoint inhibition generated enhanced and sustained antitumor immune responses with improved survival compared to adjuvant therapy (Liu J et al. Cancer Discov. 2016:1382). Clinical validation of improved outcomes with neoadjuvant compared to adjuvant immune checkpoint inhibitors has been demonstrated in trials for patients with non-small cell lung cancer, advanced melanoma, and recurrent glioblastoma (Forde, P.M., et al. N Engl J Med. 2018:1976; Amaria, R.N., et al Nat Med. 2018:1649; Cloughesy T.F., et al. Nat Med 2019:477). Recent data from a phase III trial in subjects with untreated mRCC, demonstrated the superiority of combination cabozantinib and nivolumab over sunitinib and established a new standard of care for mRCC (Choueiri T.K., et al. Annals of Onc, 2020;31 (suppl; abstr 6960). We hypothesize that if tumor specific immune responses to immunotherapy are greatest prior to nephrectomy, then treatment with nivolumab (nivo) and cabozantinib (cabo) prior to cytoreductive nephrectomy will lead to maximal peripheral and intra-tumoral specific immune responses and higher rates of CR during the course of treatment. Methods: This is an open label phase II, multicenter clinical trial of combination nivo and cabo prior to cytoreductive nephrectomy in patients with mRCC (NCT04322955). 48 treatment- naïve subjects with radiological or histological diagnosis of mRCC will be enrolled with the primary endpoint of CR rate according to RECIST version 1.1. Subjects will receive cabo (40mg) daily and nivo (480mg) every 4 weeks for 12 weeks prior to nephrectomy and a 3+3 design will be used to evaluate the safety of the interval (21 or 14 days) between the discontinuation of cabo and nephrectomy. Post-operatively, subjects will resume treatment with cabo and nivo until evidence of disease progression. Secondary endpoints include median size reduction of the primary tumor, response rate, PFS, OS, and surgical outcomes using the Clavien-Dindo classification system. Tissue based assays will quantify treatment related changes in the renal tumor microenvironment through polychromatic immunofluorescence, single cell RNA sequencing of the biopsy and nephrectomy specimen, and multiplex assessment of circulating serum cytokines. Dynamic contrast-enhanced MRI will be performed in a subset of subjects to assess radiologic correlates of response. The study is currently open to enrollment. Clinical trial information: NCT04322955.

Phase III study of local or systemic therapy INtensification DIrected by PET in prostate CAncer patients with post-prostaTEctomy biochemical recurrence (INDICATE): ECOG-ACRIN EA8191.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS5098-TPS5098
Author(s):  
Neha Vapiwala ◽  
Yu-Hui Chen ◽  
Steve Y. Cho ◽  
Fenghai Duan ◽  
Christos Kyriakopoulos ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Systemic Therapy ◽  
Biochemical Recurrence ◽  
Radiographic Progression ◽  
Systemic Treatment ◽  
Phase Iii ◽  
Type I ◽  
Treatment Intensification ◽  
Free Survival ◽  
Prostate Bed

TPS5098 Background: Radiation therapy (RT) to the prostate bed and pelvic nodes with short-term androgen deprivation therapy (STAD) is considered a standard of care (SOC) salvage therapy (ST) paradigm for prostate cancer (PC) patients (pts) with post-prostatectomy (RP) biochemical recurrence (BCR). Fluciclovine-PET/CT imaging is FDA-approved in this setting, with improved accuracy for detection of metastases not identified with conventional imaging (CIM). Given PET's greater sensitivity and specificity, its findings are increasingly but variably applied to justify modification or omission of SOC therapies without high-level evidence of clinical benefit. PET may help identify candidates for local or systemic treatment intensification of the otherwise non-tailored SOC approach. Improved systemic control and disease detection with molecular imaging have led to increasing use of focally ablative metastasis-directed RT, to delay or enhance systemic therapy through increased local control. There is also interest in earlier use of systemic therapy; apalutamide (Apa) is a nonsteroidal antiandrogen with established efficacy in improving overall and radiographic progression-free survival (PFS) for non-metastatic castration-resistant and metastatic castration-sensitive PC. This study will evaluate whether pts with PET-detected lesions benefit from such local or systemic treatment intensification approaches. Methods: PC pts with post-RP BCR (PSA>0.5ng/mL; >0.2ng/mL if within 12 mos of RP) and no metastases on CIM who are candidates for SOC ST (RT to prostate bed and pelvic nodes with STAD) are eligible. Prior to study registration, pts undergo SOC baseline PET (18F-fluciclovine but PSMA radiotracers permitted pending commercial availability). Based on institutional clinical interpretation of the SOC PET, pts will be placed in Cohort 1 (PET-negative) or 2 (PET-positive for extra-pelvic metastases). Cohort 1 will be randomized to SOC ST +/- Apa for 6 months and Cohort 2 will be randomized to SOC ST and Apa +/- metastasis-directed RT to PET-positive lesions. The primary endpoint is PFS, defined as time from randomization to radiographic progression on CIM, symptomatic disease or death. Primary objectives are to evaluate whether addition of Apa to SOC ST and addition of metastasis-directed RT to SOC ST and Apa could prolong PFS in Cohorts 1 and 2, respectively. For Cohort 1, 480 pts will be randomized with 85% power to distinguish 5-year PFS rate of 90% (Apa arm) vs. 80% (SOC arm) using one-sided stratified log-rank test with type I error of 0.025. For Cohort 2, 324 pts will be randomized with 85% power to distinguish 5-year PFS rate of 76.5% in the experimental arm from 61.5% in the control arm. Secondary endpoints include overall and event-free survival, toxicity, and PET progression. Clinical trial information: NCT04423211.

Phase II trial of cytoreductive surgery in kidney cancer plus immunotherapy (nivolumab) and targeted kinase inhibition (cabozantinib) (Cyto-KIK).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. TPS371-TPS371
Author(s):  
Karie Runcie ◽  
Eric A. Singer ◽  
Moshe Chaim Ornstein ◽  
Christopher B. Anderson ◽  
Matthew Dallos ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Phase Ii ◽  
Checkpoint Inhibitors ◽  
Recurrent Glioblastoma ◽  
Phase Iii ◽  
Cytoreductive Nephrectomy ◽  
Open Label ◽  
Orthotopic Mouse Model

TPS371 Background: Despite recent therapeutic advancements in metastatic renal cell carcinoma (mRCC), only 5-10% of patients will achieve a complete response (CR) to therapy. Cytoreductive nephrectomy removes a large portion of the tumor which may be a source of immunosuppression driven by tumor cell-intrinsic factors in the tumor microenvironment. A pre-clinical orthotopic mouse model of aggressive metastatic triple negative breast cancer showed that neoadjuvant anti-PD-1 checkpoint inhibition generated enhanced and sustained antitumor immune responses with improved survival compared to adjuvant therapy (Liu J et al. Cancer Discov. 2016:1382). Clinical validation of improved outcomes with neoadjuvant compared to adjuvant immune checkpoint inhibitors has been demonstrated in trials for patients with non-small cell lung cancer, advanced melanoma, and recurrent glioblastoma (Forde, P.M., et al. N Engl J Med. 2018:1976; Amaria, R.N., et al Nat Med. 2018:1649; Cloughesy T.F., et al. Nat Med 2019:477). Recent data from a phase III trial in subjects with untreated mRCC, demonstrated the superiority of combination cabozantinib and nivolumab over sunitinib and established a new standard of care for mRCC (Choueiri T.K., et al. Annals of Onc, 2020;31 (suppl; abstr 6960). We hypothesize that if tumor specific immune responses to immunotherapy are greatest prior to nephrectomy, then treatment with nivolumab (nivo) and cabozantinib (cabo) prior to cytoreductive nephrectomy will lead to maximal peripheral and intra-tumoral specific immune responses and higher rates of CR during the course of treatment. Methods: This is an open label phase II, multicenter clinical trial of combination nivo and cabo prior to cytoreductive nephrectomy in patients with mRCC (NCT04322955). 48 treatment- naïve subjects with radiological or histological diagnosis of mRCC will be enrolled with the primary endpoint of CR rate according to RECIST version 1.1. Subjects will receive cabo (40mg) daily and nivo (480mg) every 4 weeks for 12 weeks prior to nephrectomy and a 3+3 design will be used to evaluate the safety of the interval (21 or 14 days) between the discontinuation of cabo and nephrectomy. Post-operatively, subjects will resume treatment with cabo and nivo until evidence of disease progression. Secondary endpoints include median size reduction of the primary tumor, response rate, PFS, OS, and surgical outcomes using the Clavien-Dindo classification system. Tissue based assays will quantify treatment related changes in the renal tumor microenvironment through polychromatic immunofluorescence, single cell RNA sequencing of the biopsy and nephrectomy specimen, and multiplex assessment of circulating serum cytokines. Dynamic contrast-enhanced MRI will be performed in a subset of subjects to assess radiologic correlates of response. The study is currently open to enrollment. Clinical trial information: AAAS6927 .

scholarly journals A Review of Phase III Clinical Trials of Prostate Cancer Chemoprevention

2007 ◽  
Vol 89 (3) ◽  
pp. 207-211 ◽  
Author(s):  
JF Thorpe ◽  
S Jain ◽  
TH Marczylo ◽  
AJ Gescher ◽  
WP Steward ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Cancer Prevention ◽  
Age Of Onset ◽  
Cancer Chemoprevention ◽  
Phase Iii ◽  
Phase Iii Clinical Trials ◽  
Prostate Cancer Prevention ◽  
Phase Iii Trials

INTRODUCTION Prostate cancer is an excellent target for chemoprevention strategies; given its late age of onset, any delay in carcinogenesis would lead to a reduction in its incidence. This article reviews all the completed and on-going phase III trials in prostate cancer chemoprevention. PATIENTS AND METHODS All phase III trials of prostate cancer chemoprevention were identified within a Medline search using the keywords ‘clinical trial, prostate cancer, chemoprevention’. RESULTS In 2003, the Prostate Cancer Prevention Trial (PCPT) became the first phase III clinical trial of prostate cancer prevention. This landmark study was terminated early due to the 24.8% reduction of prostate cancer prevalence over a 7-year period in those men taking the 5α-reductase inhibitor, finasteride. This article reviews the PCPT and the interpretation of the excess high-grade prostate cancer (HGPC) cases in the finasteride group. The lack of relationship between cumulative dose and the HGPC cases, and the possible sampling error of biopsies due to gland volume reduction in the finasteride group refutes the suggestion that this is a genuine increase in HGPC cases. The other on-going phase III clinical trials of prostate cancer chemoprevention – the REDUCE study using dutasteride, and the SELECT study using vitamin E and selenium – are also reviewed. CONCLUSIONS At present, finasteride remains the only intervention shown in long-term prospective phase III clinical trials to reduce the incidence of prostate cancer. Until we have the results of trials using alternative agents including the on-going REDUCE and SELECT trials, the advice given to men interested in prostate cancer prevention must include discussion of the results of the PCPT. The increased rate of HGPC in the finasteride group continues to generate debate; however, finasteride may still be suitable for prostate cancer prevention, particularly in men with lower urinary tract symptoms.

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.

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