scholarly journals Novel hormonal agents for metastatic Castration-Resistant Prostate Cancer: comparing outcomes. A single-center retrospective study

2021 ◽  
Vol 93 (4) ◽  
pp. 393-398
Author(s):  
Roberto Saldanha Jarimba ◽  
Miguel Nobre Eliseu ◽  
João Pedroso Lima ◽  
Vasco Quaresma ◽  
Pedro Moreira ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Response Rate ◽  
Statistical Significance ◽  
Biochemical Response ◽  
Castration Resistant Prostate Cancer ◽  
Radiological Progression ◽  
Castration Resistant ◽  
Primary Endpoints ◽  
Biochemical Progression

Introduction: Prostate cancer is the most common cancer in men, accounting for 15% of all diagnosed cancers and is the sixth leading cause of cancerrelated deaths amongst men worldwide. Abiraterone and enzalutamide were the first two novel hormonal agents approved for the treatment of metastatic prostate cancer but there is a lack of quality evidence regarding which is associated with better outcomes and who would benefit the most with one or another of these drugs. Objective: To evaluate the clinical outcomes of real-world patients submitted to treatment with novel hormonal agents, enzalutamide and abiraterone, for castration resistant metastatic prostate cancer in an academic center.Patients and methods: We retrospectively reviewed patients treated for castration-resistant prostate cancer with either abiraterone or enzulatamide between January 1, 2016 and December 31, 2019. The primary endpoints were biochemical response, biochemical progression, radiological progression, clinical deterioration (attributed to disease progression) and death. Results: Enzalutamide had a higher biochemical response rate than abiraterone in patients with mCRPC (77.1% vs 58.1%, p = 0.016). Achieving a biochemical response was associated with a lower risk of biochemical progression (OR: 0.248, p = 0.017) and death (OR: 0.302, p = 0.038). Conclusions: Enzalutamide conferred higher biochemical response rate than abiraterone in patients with mCRPC. Despite the trend to better performance of other endpoints in the enzalutamide group, it did not achieve statistical significance. Well-designed prospective studies are needed to elucidate the comparative efficacies of these agents.

scholarly journals Oncological Response and Predictive Biomarkers for the Checkpoint Inhibitors in Castration-Resistant Metastatic Prostate Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 (1) ◽  
pp. 8
Author(s):  
Omar Fahmy ◽  
Nabil A. Alhakamy ◽  
Mohd G. Khairul-Asri ◽  
Osama A. A. Ahmed ◽  
Usama A. Fahmy ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Metastatic Prostate Cancer ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Castration Resistant Prostate Cancer ◽  
Overall Response ◽  
Castration Resistant

Recently, checkpoint inhibitors have been investigated in metastatic prostate cancer, however their overall effect is unclear and needs to be further investigated. Objectives: The aim of this systematic review is to investigate the oncological response of metastatic castration-resistant prostate cancer patients to immune checkpoint inhibitors. Methods: Based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement, a systematic review of the literature was conducted through online electronic databases and the American Society of Clinical Oncology (ASCO) Meeting Library. Eligible publications were selected after a staged screening and selection process. RevMan 5.4 software was employed to run the quantitative analysis and forest plots. Risk of bias assessment was conducted using the Cochrane tool and Newcastle–Ottawa Scale for the randomized and non-randomized trials, respectively. Results: From the 831 results retrieved, 8 studies including 2768 patients were included. There was no significant effect on overall survival (OS) (overall response (OR) = 0.98; Z = 0.42; p = 0.67). Meanwhile, progression-free survival (PFS) was significantly better with immune checkpoint inhibitors administration (OR = 0.85; Z = 3.9; p < 0.0001). The subgroup analysis for oncological outcomes based on programmed death ligand 1 (PD-L1) positivity status displayed no significant effect, except on prostate-specific antigen response rate (PSA RR) (OR = 3.25; Z = 2.29; p = 0.02). Based on DNA damage repair (DDR), positive patients had a significantly better PFS and a trend towards better OS and overall response rate (ORR); the ORR was 40% in positive patients compared to 20% in the negative patients (OR = 2.46; Z = 1.3; p = 0.19), while PSA RR was 23.5% compared to 14.3% (OR = 1.88; Z = 0.88; p = 0.38). Better PFS was clearly associated with DDR positivity (OR = 0.70; Z = 2.48; p = 0.01) with a trend towards better OS in DDR positive patients (OR = 0.71; Z = 1.38; p = 0.17). Based on tumor mutation burden (TMB), ORR was 46.7% with high TMB versus 8.8% in patients with low TMB (OR = 11.88; Z = 3.0; p = 0.003). Conclusions: Checkpoint inhibitors provide modest oncological advantages in metastatic castration-resistant prostate cancer. There are currently no good predictive indicators that indicate a greater response in some patients.

scholarly journals PSMA Expression Predicts Early Biochemical Response in Patients with Metastatic Castration-Resistant Prostate Cancer under 177Lu-PSMA-617 Radioligand Therapy

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2938
Author(s):  
Liam Widjaja ◽  
Rudolf A. Werner ◽  
Tobias L. Ross ◽  
Frank M. Bengel ◽  
Thorsten Derlin
Keyword(s):  
Prostate Cancer ◽  
Whole Body ◽  
Biochemical Response ◽  
Clinical Parameters ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Castration Resistant ◽  
Psa Response ◽  
High Age ◽  
Psma Expression

177Lu-Prostate-specific membrane antigen (PSMA)-radioligand therapy (RLT) is a promising treatment option in patients with metastatic castration-resistant prostate cancer (mCRPC). We aimed to determine the predictive value of pretherapeutic PSMA-ligand positron emission tomography (PET) and established clinical parameters for early biochemical response after two cycles of RLT. In total, 71 mCRPC patients who had undergone PET/computed tomography (CT) with 68Ga-PSMA-11 prior to two cycles of 177Lu-PSMA-617 RLT were included. Malignant lesions on pretherapeutic PET/CTs were manually segmented and average maximum PSMA expression (maximum standardized uptake values, SUVmax), whole-body PSMA-tumor volume (TV), and whole-body total lesion (TL)-PSMA were calculated. We then tested the predictive performance of these parameters for early biochemical response (defined as prostate-sepcific antigen (PSA) decrease of ≥50% according to PCWG2) after two cycles of RLT, relative to established clinical parameters. Early PSA response was observed in 34/71 patients. PSA change after two cycles of RLT correlated with pretherapeutic SUVmax (r = −0.49; p < 0.001), but not with PSMA-TV (r = 0.02; p = 0.89) or TL-PSMA (r = −0.15; p = 0.22). A cut-off of 19.8 for SUVmax and 75.5 years for age was defined by receiver operating characteristics and revealed a significant outcome difference for early biochemical response between patients with adversely low vs. high PSMA expression and low vs. high age (p < 0.001). Multivariate analysis identified SUVmax (HR, 7.94, p = 0.001) and age (HR, 8.05, p = 0.002) as independent predictors for PSA response early in the treatment course. Thus, high age and high PSMA expression in patients scheduled for RLT identify patients with early biochemical response. This study provides a rationale for further prospective studies exploring PET-guided treatment intensification in selected patients.

Sex Hormones and Prostate Cancer

2020 ◽  
Vol 71 (1) ◽  
pp. 33-45 ◽  
Author(s):  
Richard J. Auchus ◽  
Nima Sharifi
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Current Treatment ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
History Of ◽  
Prostate Cancer Research ◽  
Prostate Cancers ◽  
Androgen Independent ◽  
Transition Studies

The prostate is an androgen-dependent organ that develops only in male mammals. Prostate cancer is the most common nonskin malignancy in men and the second leading cause of cancer deaths. Metastatic prostate cancer initially retains its androgen dependence, and androgen-deprivation therapy often leads to disease control; however, the cancer inevitably progresses despite treatment as castration-resistant prostate cancer, the lethal form of the disease. Although it was assumed that the cancer became androgen independent during this transition, studies over the last two decades have shown that these tumors evade treatment via mechanisms that augment acquisition of androgens from circulating precursors, increase sensitivity to androgens and androgen precursors, bypass the androgen receptor, or a combination of these mechanisms. This review summarizes the history of prostate cancer research leading to the contemporary view of androgen dependence for prostate cancers and the current treatment approaches based on this modern paradigm.

scholarly journals Predictors for progression of metastatic prostate cancer to castration-resistant prostate cancer in Indians

2016 ◽  
Vol 143 (7) ◽  
pp. 68
Author(s):  
Anil Mandhani ◽  
SanjoyKumar Sureka ◽  
Ruchir Maheshwari ◽  
Shalini Agnihotri ◽  
Nilay Mitash ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

Use of epirubicin, carboplatin, and 5-fluorouracil (ECarboF) as a second-line treatment in metastatic castration-resistant prostate cancer.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 173-173
Author(s):  
U. B. McGovern ◽  
S. J. Harland
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Performance Status ◽  
Median Number ◽  
Second Line ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Castration Resistant ◽  
Docetaxel Chemotherapy ◽  
Line Chemotherapy

173 Background: ECarboF chemotherapy is an active first line chemotherapy treatment for metastatic prostate cancer. We have now investigated its efficacy and toxicity in patients who have progressed during or after docetaxel chemotherapy. Methods: 37 patients with metastatic prostate cancer who had received ECarboF chemotherapy were retrospectively reviewed from a five year period (2005-2010). All patients had previously received first-line docetaxel chemotherapy and had either progressed following treatment (n=17) or were docetaxel refractory (n=20). Patients received epirubicin 50mg/m2 iv d1, carboplatin (AUC 5) d1, fluorouracil 440mg/m2 d1, d15 and folinic acid 20mg/m2 d1, d15 on a q4w cycle. 20% dose reductions were made for the first cycle in patients with poorer performance status. PSA was measured before each cycle of treatment and all patients were assessed for toxicity. Results: Patients had a median age of 70 years (range 48-77), median baseline PSA of 226.5 ng/mL (range 9.6-1,580) and the median number of ECarboF chemotherapy cycles received was 6 (range 1-10). 65% (n=24) of patients were ECOG 0-1, the remaining 35% (n=13) were ECOG 2-3. 16% (n=6) patients had a ≥ 30% decline in PSA and 16% (n=6) patients had a ≥ 50% decline in PSA. 35% (n=13) of patients experienced grade 3/4 toxicity, most commonly anaemia (13.5%), neutropenia (13.5%) and thrombocytopenia (8.1%) with one treatment related death (neutropenic sepsis) during the five year period analysed. Median time to PSA progression was 5.1 months. Conclusions: ECarboF has activity with acceptable toxicity post docetaxel in the treatment of metastatic castration resistant prostate cancer. Although PSA response rates are modest, the time to progression is comparable to that of more toxic regimens. ECarboF should be considered as an active second-line chemotherapy regimen. No significant financial relationships to disclose.

Immunological and genomic correlates of response to anti-PD1 checkpoint therapy in mismatch proficient and deficient patients with metastasized castration resistant prostate cancer.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 248-248 ◽  
Author(s):  
Minke Smits ◽  
Maarten Johannes van der Doelen ◽  
Harm Westdorp ◽  
Inge M. van Oort ◽  
Michiel Sedelaar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Progression Free Survival ◽  
Computational Prediction ◽  
Cell Receptor ◽  
Castration Resistant Prostate Cancer ◽  
Radiological Progression ◽  
Free Survival ◽  
Immune Correlates ◽  
Castration Resistant ◽  
Immune Oncology

248 Background: Response to anti-PD1/PDL1 checkpoint therapy has been witnessed in only a minority of patients with castration-resistant prostate cancer (CRPC). Microsatellite instability (MSI) is the only biomarker predictive of response; additional immune and genomic correlates are needed to improve the proportion of patients that may benefit from checkpoint immunotherapy. Methods: CRPC patients were treated with anti-PD1 checkpoint immunotherapy in two basket-studies, depending on PDL1-positivity ( > 1%) or presence of MSI, and consented to prospective immune-oncology biomarker study. Genomic and immune correlates of response were studied in both MSI as microsatellite stable CRPC patients, and included PDL1 expression , whole genome sequencing on a baseline fresh metastatic biopsy, tumor microenvironment (immuno)profiling using multi-color immunohistochemistry, computational prediction of neoantigens, T-cell receptor sequencing and MHC-tetramer staining. Response was evaluated according to PCWG3 criteria and treatment was continued until radiological progression with lack of clinical benefit or toxicity. Results: At present 11 CRPC patients were included in the program and treated with nivolumab (n = 4) and pembrolizumab (n = 7). Treatment is currently ongoing in 7/11 (64%) of patients, with treatment discontinuation due to immune-related colitis (n = 2) and disease progression (n = 2). Biochemical PSA ( > 50%) responses were seen in both MSI and PDL1 positive patients. Median progression-free survival has not yet been reached. Translational studies on genomic and immune correlates of response will be presented in detail. Conclusions: Encouraging responses to anti-PD1 checkpoint immunotherapy were seen in CRPC patients selected for PDL1-positivity and MSI. An integrative biomarker suite will likely be needed to predict response to anti-PD1 therapy in CRPC.

Personalized use of metronomic cyclophosphamide for DNA repair deficient castration-resistant prostate cancer: A phase II trial.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. TPS346-TPS346
Author(s):  
Cameron Phillips ◽  
Giulio Francia ◽  
Robert S. Kerbel ◽  
Urban Emmenegger
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Type I ◽  
Similar Response ◽  
Castration Resistant Prostate Cancer ◽  
Phase Ii Trials ◽  
Castration Resistant

TPS346 Background: There is a continued need to identify novel targets for the treatment of metastatic, castration-resistant prostate cancer (mCRPC). DNA damage repair (DDR) aberrations are emerging as such a target: 20%-30% of mCRPCs harbor DDR gene aberrations, rendering tumors particularly sensitive to DNA damaging agents and poly ADP-ribose polymerase inhibitor (PARPi) therapy. 88% of men with DDR deficient mCRPC responded to the PARPi olaparib in a phase II trial, whereas in unselected mCRPC patients the metronomic use of the DNA damaging agent cyclophosphamide (CPA) resulted in response rates of 25-60%. Intriguingly, in randomized phase II trials of unselected ovarian and triple-negative breast cancer (ie tumor types enriched for DDR defects), metronomic CPA alone was as active as metronomic CPA plus the PARPi veliparib. Based on this we hypothesize that DDR deficient mCRPC is particularly sensitive to metronomic CPA. To the best of our knowledge this is the first attempt to utilize metronomic CPA in a personalized manner. Our study has the potential to define metronomic CPA as an affordable and well-tolerated alternative to PARPi therapy in men with DDR deficient mCRPC. Methods: To study if metronomic CPA achieves a similar response rate (ie ≥85%) in DDR deficient mCRPC as seen with olaparib, men with mCRPC progressing after 1-2 lines of systemic therapy will undergo circulating tumor DNA based testing for BRCA1/2 or ATM aberrations. Patients with such aberrations will proceed with metronomic CPA (50 mg po daily). Primary endpoint: RECIST 1.1 and/or ≥50% PSA response rate at 12 weeks. Secondary endpoints include biochemical, radiological and clinical progression-free survival. Applying the Optimal Simon's Two-Stage design, and using a type I error rate of 0.05 and a power of 0.8, in the first stage we plan to enroll 14 patients. If there are ≤10 or fewer responses, the study will be stopped. Otherwise, another 19 patients will be accrued as part of the second stage.

The effect of AKR1C3 on the switch from prednisone to dexamethasone in metastatic castration-resistant prostate cancer patients receiving abiraterone.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 133-133
Author(s):  
Yuchao Ni ◽  
Jinge Zhao ◽  
Junru Chen ◽  
Guangxi Sun ◽  
Sha Zhu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Free Survival ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Psa Progression ◽  
Biochemical Progression ◽  
First Line Treatment

133 Background: Abiraterone is the first-line treatment for men with metastatic castration-resistant prostate cancer (mCRPC) and is recommended to be used with prednisone. Previous studies had demonstrated that the switch from prednisone to dexamethasone in some mCRPC patients can reverse abiraterone-resistance. However, it remains uncertain which group of patients will benefit from such switching. AKR1C3 is a critical enzyme contributing to the drug-resistance of abiraterone. Here, we aim to explore the significance of AKR1C3 in predicting the therapeutic efficacy of the corticosteroid switching in mCRPC patients receiving abiraterone. Methods: In total, 43 PCa patients treated with abiraterone after mCRPC between 2016 and 2018 in our institution were included. After biochemical progression in abiraterone plus prednisone, all cases received a corticosteroid switch to abiraterone plus dexamethasone. The expression of AKR1C3 was detected by immunohistochemical staining from re-biopsy (re‐Bx) of primary prostate lesions at the time of mCRPC. Kaplan‐Meier curves were used to analyze the association between AKR1C3 and treatment outcomes. Results: Totally, AKR1C3 was positive in 19 of 43 (44.19%) cases. In the corticosteroid switch treatment, 30% PSA decline was confirmed in 18/43 (41.86%) patients, while the median PSA progression‐free survival (PSA-PFS) and overall survival (OS) was 4.93 Mo and 31.57 Mo, respectively in the whole cohort. AKR1C3 expression was associated with statistically shorter median PSA-PFS (4.50 Mo vs 7.73 Mo; p =0.010) and numerically lower median OS (25.43 Mo vs 39.37 Mo, p =0.274). While the 30% PSA decline rate was numerically comparable between those with and without AKR1C3 expression (31.6% vs 50.0%, p =0.224). Conclusions: This study showed AKR1C3 detection in tissues from prostate re‐Bx at mCRPC was associated with poor PSA-PFS in the corticosteroid switch from abiraterone plus prednisone to abiraterone plus dexamethasone. These results would be helpful in making optimal personalized treatment decisions for patients with mCRPC, facilitating physicians predicting the effectiveness of corticosteroid switch treatment.

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