scholarly journals Cabazitaxel versus abiraterone or enzalutamide in metastatic castration-resistant prostate cancer: post hoc analysis of the CARD study excluding chemohormonal therapy for castrate-naive disease

2021 ◽  
Author(s):  
Hiroyoshi Suzuki ◽  
Daniel Castellano ◽  
Johann de Bono ◽  
Cora N Sternberg ◽  
Karim Fizazi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Events ◽  
Clinical Outcomes ◽  
Specific Antigen ◽  
Tumour Response ◽  
Progression Free Survival ◽  
Median Number ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Number Of Cycles

Abstract Background In the CARD study (NCT02485691), cabazitaxel significantly improved clinical outcomes versus abiraterone or enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel and the alternative androgen-signalling-targeted inhibitor. However, some patients received docetaxel or the prior alternative androgen-signalling-targeted inhibitor in the metastatic hormone-sensitive (mHSPC) setting. Therefore, the CARD results cannot be directly translated to a Japanese population. Methods Patients (N = 255) received cabazitaxel (25 mg/m2 IV Q3W, prednisone, G-CSF) versus abiraterone (1000 mg PO, prednisone) or enzalutamide (160 mg PO) after prior docetaxel and progression ≤12 months on the alternative androgen-signalling-targeted inhibitor. Patients who received combination therapy for mHSPC were excluded (n = 33) as docetaxel is not approved in this setting in Japan. Results A total of 222 patients (median age 70 years) were included in this subanalysis. Median number of cycles was higher for cabazitaxel versus androgen-signalling-targeted inhibitors (7 versus 4). Clinical outcomes favoured cabazitaxel over abiraterone or enzalutamide including, radiographic progression-free survival (rPFS; median 8.2 versus 3.4 months; P < 0.0001), overall survival (OS; 13.9 versus 11.8 months; P = 0.0102), PFS (4.4 versus 2.7 months; P < 0.0001), confirmed prostate-specific antigen response (37.0 versus 14.4%; P = 0.0006) and objective tumour response (38.9 versus 11.4%; P = 0.0036). For cabazitaxel versus androgen-signalling-targeted inhibitor, grade ≥ 3 adverse events occurred in 55% versus 44% of patients, with adverse events leading to death on study in 2.7% versus 5.7%. Conclusions Cabazitaxel significantly improved outcomes including rPFS and OS versus abiraterone or enzalutamide and are reflective of the Japanese patient population. Cabazitaxel should be considered the preferred treatment option over abiraterone or enzalutamide in this setting.

scholarly journals Combined CTLA-4 and PD-L1 blockade in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer is associated with increased myeloid and neutrophil immune subsets in the bone microenvironment

2021 ◽  
Vol 9 (10) ◽  
pp. e002919
Author(s):  
Sumit K Subudhi ◽  
Bilal A Siddiqui ◽  
Ana M Aparicio ◽  
Shalini S Yadav ◽  
Sreyashi Basu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Events ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Immune Checkpoints ◽  
Castration Resistant Prostate Cancer ◽  
Bone Microenvironment ◽  
Castration Resistant ◽  
Number Of Patients ◽  
Measurable Disease

BackgroundImmune checkpoint therapy (ICT) has low response rates in patients with metastatic castration-resistant prostate cancer (mCRPC), in part due to few T cells in the tumor microenvironment (TME). Anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) promotes intratumoral T cell infiltration but induces upregulation of PD-1 and programmed death ligand-1 (PD-L1) within the prostate TME. Combined anti-CTLA-4 plus anti-PD-1 can partly overcome this adaptive resistance and was recently shown to augment responses in patients with mCRPC with measurable disease. Although bone is the most common site of metastasis in prostate cancer, patients with bone-predominant disease are frequently excluded from trials because they lack measurable disease, which limits assessment of disease progression and tissue sampling. We therefore designed this study to investigate combined ICT in mCRPC to bone.HypothesisCombined anti-CTLA-4 (tremelimumab) plus anti-PD-L1 (durvalumab) is safe and well tolerated in patients with chemotherapy-naïve mCRPC to bone.Patients and methodsIn this single-arm pilot study, men with chemotherapy-naïve mCRPC to bone received tremelimumab (75 mg intravenous) plus durvalumab (1500 mg intravenous) every 4 weeks (up to four doses), followed by durvalumab (1500 mg intravenous) maintenance every 4 weeks (up to nine doses). The primary endpoint was incidence of adverse events. Secondary endpoints included serum prostate-specific antigen (PSA), progression-free survival (PFS), radiographic PFS (rPFS), and maximal PSA decline.ResultsTwenty-six patients were treated between August 8, 2017 and March 28, 2019. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 11 patients (42%), with no grade 4 or 5 events. TRAEs leading to discontinuation occurred in three patients (12%). PSA decline ≥50% occurred in three patients (12%). Six patients (24%) achieved stable disease for >6 months. At a median follow-up of 43.6 months, median rPFS was 3.7 months (95% CI: 1.9 to 5.7), and median overall survival was 28.1 months (95% CI: 14.5 to 37.3). Post-treatment evaluation of the bone microenvironment revealed transcriptional upregulation in myeloid and neutrophil immune subset signatures and increased expression of inhibitory immune checkpoints.ConclusionsTremelimumab plus durvalumab was safe and well tolerated in patients with chemotherapy-naïve mCRPC to bone, with potential activity in a small number of patients as measured by rPFS. Combination of CTLA-4 and PD-L1 blockade with therapies targeting the myeloid compartment or other inhibitory immune receptors may be necessary to overcome mechanisms of resistance within prostate bone microenvironment.Trial registration numberNCT03204812.

scholarly journals Cabazitaxel for Metastatic Castration-Resistant Prostate Cancer: Retrospective Data Analysis from an Indian Centre

2016 ◽  
Vol 9 (2) ◽  
pp. 506-515
Author(s):  
Vanita Noronha ◽  
Amit Joshi ◽  
Vamshi Krishna Muddu ◽  
Vijay Maruti Patil ◽  
Kumar Prabhash
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Retrospective Data Analysis ◽  
Grade 3 ◽  
Named Patient Programme

Objective: To determine the efficacy and safety of cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC) patients from the named patient programme (NPP) at our centre. Methods: mCRPC patients who progressed on docetaxel were given cabazitaxel intravenously every 3 weeks until disease progression or unacceptable toxicity occurred. Overall survival, progression-free survival, prostate-specific antigen response, quality of life (QOL) changes, and safety were reported. Results: Nine men received cabazitaxel (median: 7 cycles; range: 1–27) under the NPP and were followed until death. Median survival was 14.07 months (1.07–23.80) and progression-free survival was 2.67 months (1.07–20.27). QOL was stable for most patients. Common adverse events (grade ≥3) were neutropenia (n = 8), anaemia (n = 4), and leucopenia (n = 4). Conclusion: These data from 9 patients are consistent with the results reported in the TROPIC study with a manageable safety profile.

scholarly journals A prognostic model for stratifying clinical outcomes in chemotherapy-naive metastatic castration-resistant prostate cancer patients treated with abiraterone acetate

2017 ◽  
Vol 12 (2) ◽  
pp. E47-52 ◽  
Author(s):  
Daniel Joseph Khalaf ◽  
Claudia M. Avilés ◽  
Arun A. Azad ◽  
Katherine Sunderland ◽  
Tilman Todenhöfer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcomes ◽  
Group Performance ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Prognostic Index ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Progression

Introduction: Recently, a prognostic index including six risk factors (RFs) (unfavourable Eastern Cooperative Oncology Group performance status [ECOG PS], presence of liver metastases, short response to luteinizing hormone-releasing hormone [LHRH] agonists/ antagonists, low albumin, increased alkaline phosphatase [ALP] and lactate dehydrogenase [LDH]) was developed from the COUAA- 301 trial in post-chemotherapy metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate. Our primary objective was to evaluate this model in a cohort of chemotherapy-naive mCRPC patients receiving abiraterone.Methods: We identified 197 chemotherapy-naive patients who received abiraterone at six BC Cancer Agency centres and who had complete information on all six RFs. Study endpoints were prostate-specific antigen (PSA) response rate (RR), time to PSA progression, time on treatment, and overall survival (OS). PSA RR and survival outcomes were compared using Χ2 test and log-rank test. Multivariable Cox proportional hazard analysis was performed to identify RFs independently associated with OS.Results: Patients were classified into good (0‒1 RFs), intermediate (2‒3 RFs), and poor (4‒6 RFs) prognostic groups (33%, 52%, and 15%, respectively). For good-, intermediate-, and poor-risk patients, PSA RR (≥50% decline) was 60% vs. 42% vs. 40% (p=0.05); median time to PSA progression was 7.3 vs. 5.3 vs. 5.0 months (p=0.02); and median OS was 29.4 vs. 13.8 vs. 8.7 months (p<0.0001).Conclusions: The six-factor prognostic index model stratifies clinical outcomes in chemotherapy-naive mCRPC patients treated with abiraterone. Identifying patients at risk of poor outcome is important for informing clinical practice and clinical trial design.

Low-Dose Docetaxel Combined with Dexamethasone Is Feasible for Patients with Castration-Resistant Prostate Cancer

Chemotherapy ◽  
2015 ◽  
Vol 61 (1) ◽  
pp. 23-31 ◽  
Author(s):  
Noriyoshi Miura ◽  
Nozomu Tanji ◽  
Yutaka Yanagihara ◽  
Terutaka Noda ◽  
Seiji Asai ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Low Dose ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Hematological Toxicity ◽  
Castration Resistant Prostate Cancer ◽  
Gastric Bleeding ◽  
Castration Resistant ◽  
Analgesic Agents ◽  
Grade 3

Aim: Docetaxel-based chemotherapy against castration-resistant prostate cancer (CRPC) has recently been shown to be effective and tolerable. The objective of this study was to retrospectively evaluate the efficacy and toxicity of low-dose docetaxel in combination with dexamethasone. Methods: Thirty-seven CRPC patients were administered a treatment regimen consisting of 50 mg/m2 docetaxel once every 3-4 weeks and 1 mg dexamethasone daily at our institution, between November 2004 and April 2014. Results: Twenty-four patients (65%) had a decrease in serum prostate-specific antigen (PSA) >50%. The median overall survival (OS) and PSA progression-free survival were 26.2 and 10.0 months, respectively. Ten of 12 patients (83%) taking analgesic agents reduced their intake because of decreased pain levels. Grade 3 febrile neutropenia occurred in 2 patients (5%). Nonhematological toxicities were less frequent but sometimes severe. Treatment-related death occurred in 2 octogenarian patients, 1 due to gastric bleeding and the other due to infective endocarditis. Conclusion: Low-dose docetaxel in combination with dexamethasone is feasible in Japanese CRPC patients. Hematological toxicity is less than that seen with standard docetaxel therapy, but it is necessary to monitor patients for severe nonhematological toxicities, particularly very elderly patients.

scholarly journals Safety and Efficacy of First-Line Treatments for Chemotherapy-Naive Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Indirect Comparison

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Haofeng Zheng ◽  
Jialiang Chen ◽  
Wenhan Qiu ◽  
Sijie Lin ◽  
Yanxiong Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Specific Antigen ◽  
Indirect Comparison ◽  
Progression Free Survival ◽  
Optimal Order ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Safety And Efficacy ◽  
Castration Resistant

Recently, several drugs have been introduced for the first-line treatment of chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC), but few studies have compared treatment outcomes directly. This indirect comparison among 10 clinical trials (n= 4870 patients) retrieved from PubMed, Web of Science, Cochrane Collaboration, and ClinicalTrails.gov was performed to assess the safety and efficacy of docetaxel, cabazitaxel, abiraterone, enzalutamide, and sipuleucel-T for the initial treatment of mCRPC. No significant differences in primary outcome (overall survival) were found among initial treatments. However, docetaxel had the highest probability (37.53%) of being the most effective, but at the cost of more adverse events, while enzalutamide was associated with the best secondary outcomes (prostate-specific antigen response, progression-free survival, quality of life, and adverse event profile). Thus, docetaxel is recommended as the first agent used for the chemotherapy of mCRPC, while enzalutamide is recommended as the first nonchemotherapy treatment. Additional clinical trials are needed to confirm these findings and establish the optimal order for multidrug treatment of mCRPC.

scholarly journals Phase III Study of Cabozantinib in Previously Treated Metastatic Castration-Resistant Prostate Cancer: COMET-1

2016 ◽  
Vol 34 (25) ◽  
pp. 3005-3013 ◽  
Author(s):  
Matthew Smith ◽  
Johann De Bono ◽  
Cora Sternberg ◽  
Sylvestre Le Moulec ◽  
Stéphane Oudard ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Events ◽  
Specific Antigen ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Bone Biomarkers ◽  
End Point ◽  
Castration Resistant ◽  
Previously Treated

Purpose Cabozantinib is an inhibitor of kinases, including MET and vascular endothelial growth factor receptors, and has shown activity in men with previously treated metastatic castration-resistant prostate cancer (mCRPC). This blinded phase III trial compared cabozantinib with prednisone in patients with mCRPC. Patients and Methods Men with progressive mCRPC after docetaxel and abiraterone and/or enzalutamide were randomly assigned at a two-to-one ratio to cabozantinib 60 mg once per day or prednisone 5 mg twice per day. The primary end point was overall survival (OS). Bone scan response (BSR) at week 12 as assessed by independent review committee was the secondary end point; radiographic progression-free survival (rPFS) and effects on circulating tumor cells (CTCs), bone biomarkers, serum prostate-specific antigen (PSA), and symptomatic skeletal events (SSEs) were exploratory assessments. Results A total of 1,028 patients were randomly assigned to cabozantinib (n = 682) or prednisone (n = 346). Median OS was 11.0 months with cabozantinib and 9.8 months with prednisone (hazard ratio, 0.90; 95% CI, 0.76 to 1.06; stratified log-rank P = .213). BSR at week 12 favored cabozantinib (42% v 3%; stratified Cochran-Mantel-Haenszel P < .001). rPFS was improved in the cabozantinib group (median, 5.6 v 2.8 months; hazard ratio, 0.48; 95% CI, 0.40 to 0.57; stratified log-rank P < .001). Cabozantinib was associated with improvements in CTC conversion, bone biomarkers, and post–random assignment incidence of SSEs but not PSA outcomes. Grade 3 to 4 adverse events and discontinuations because of adverse events were higher with cabozantinib than with prednisone (71% v 56% and 33% v 12%, respectively). Conclusion Cabozantinib did not significantly improve OS compared with prednisone in heavily treated patients with mCRPC and progressive disease after docetaxel and abiraterone and/or enzalutamide. Cabozantinib had some activity in improving BSR, rPFS, SSEs, CTC conversions, and bone biomarkers but not PSA outcomes.

scholarly journals Treatment Sequences of Androgen Receptor–Targeted Agents for Prostate Cancer

2021 ◽  
Vol 1 (3) ◽  
Author(s):  
Khai Tran ◽  
Sarah McGill
Keyword(s):  
Prostate Cancer ◽  
Retrospective Study ◽  
Androgen Receptor ◽  
Clinical Outcomes ◽  
Progression Free Survival ◽  
Targeted Agents ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Treatment Sequences

No evidence was found on the treatment sequences of androgen receptor–targeted agents in patients with castration-sensitive prostate cancer. Evidence from retrospective studies, including those within a systematic review, suggests that sequential treatment of abiraterone followed by enzalutamide is more favourable than enzalutamide followed by abiraterone in improving clinical outcomes such as response rate and progression-free survival, but not overall survival, in patients with castration-resistant prostate cancer. Evidence from a retrospective study suggests that docetaxel-containing treatment sequences with androgen receptor–targeted agents may improve progression-free survival compared to sequential therapy with androgen receptor–targeted agents alone in patients with castration-resistant prostate cancer. Evidence from a retrospective study did not reveal differences in clinical outcomes of patients with castration-resistant prostate cancer treated with sequential androgen receptor–targeted agents with or without interposed chemotherapy or radium-223. These findings were in line with those observed in a 2019 CADTH report.1 However, the findings should be interpreted with caution due to low-quality evidence. No comparative cost-effectiveness studies were identified.

scholarly journals Efficacy and safety of abiraterone acetate plus prednisolone in patients with early metastatic castration-resistant prostate cancer who failed first-line androgen-deprivation therapy: a single-arm, phase 4 study

2020 ◽  
Author(s):  
K Kobayashi ◽  
N Okuno ◽  
G Arai ◽  
H Nakatsu ◽  
A Maniwa ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Androgen Deprivation Therapy ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Androgen Deprivation ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Castration Resistant

Abstract Aim The aim was to evaluate the efficacy and safety of abiraterone acetate plus prednisolone in patients with chemotherapy-naïve early metastatic castration-resistant prostate cancer who failed first-line androgen deprivation therapy. Methods Patients with early metastatic castration-resistant prostate cancer with confirmed prostate-specific antigen progression within 1-year or prostate-specific antigen progression without having normal prostate-specific antigen level (&lt;4.0 ng/mL) during first-line androgen deprivation therapy were enrolled and administered abiraterone acetate (1000 mg) plus prednisolone (10 mg). A minimum of 48 patients were required according to Simon’s minimax design. The primary endpoint was prostate-specific antigen response rate (≥50% prostate-specific antigen decline by 12 weeks), secondary endpoints included prostate-specific antigen progression-free survival and overall survival. Safety parameters were also assessed. Results For efficacy, 49/50 patients were evaluable. Median age was 73 (range: 55–86) years. The median duration of initial androgen deprivation therapy was 32.4 (range: 13.4–84.1) weeks and 48 patients experienced prostate-specific antigen progression within 1-year after initiation of androgen deprivation therapy. prostate-specific antigen response rate was 55.1% (95% confidence interval: 40.2%–69.3%), median prostate-specific antigen–progression-free survival was 24.1 weeks, and median overall survival was 102.9 weeks (95% confidence interval: 64.86 not estimable [NE]). Most common adverse event was nasopharyngitis (15/50 patients, 30.0%). The most common ≥grade 3 adverse event was alanine aminotransferase increased (6/50 patients, 12.0%). Conclusions Abiraterone acetate plus prednisolone demonstrated a high prostate-specific antigen response rate of 55.1%, suggesting tumor growth still depends on androgen synthesis in patients with early metastatic castration-resistant prostate cancer. However, prostate-specific antigen–progression-free survival was shorter than that reported in previous studies. Considering the benefit–risk profile, abiraterone acetate plus prednisolone would be a beneficial treatment option for patients with chemotherapy-naive metastatic prostate cancer who show early castration resistance.

The hematologic parameters in metastatic castration-resistant prostate cancer patients treated with abiraterone acetate.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 308-308
Author(s):  
Onal Cem ◽  
Ali Murat Sedef ◽  
Fatih KOse ◽  
Ezgi Oymak ◽  
Ozan Cem Guler ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Univariate Analysis ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Characteristic Analysis ◽  
Lymphocyte Ratio ◽  
Castration Resistant ◽  
Psa Response

308 Background: The aim of this study is to evaluate the prognostic implications of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) at baseline and after 4 and 12 weeks of treatment with abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: We retrospectively evaluated 102 mCRPC treated with abiraterone either pre- or post-chemotherapy between November 2012 and October 2017 in three institutions. We calculated NLR and PLR at baseline and at 4 and 12 weeks after initiation of abiraterone, and we evaluated prostate-specific antigen (PSA) response every 4 weeks. Fifty patients (49%) were treated with abiraterone post-docetaxel, and 52 patients (51%) received abiraterone pre-chemotherapy. Based on receiver operating characteristic analysis, patients were stratified as low NLR ( < 3.1) or high NLR (≥ 3.1), and low PLR ( < 163) or high PLR (≥ 163). The cutoff for anemia was < 12g/dL. Results: Median follow-up times for patients overall and for those who survived were 24.0 months (range, 0.3 – 54.9 months) and 25.5 months (range, 2.8 – 54.9 months), respectively. The median time of abiraterone treatment was 8.1 months (range, 2.4 – 40.1 months). The median overall survival (OS) was 20.8 months (interquartile range: 17.3–24.4). In univariate analysis, NLR, PLR, PSA response, and low hemoglobin (Hgb) were found significantly predictive of OS and progression-free survival (PFS). In multivariate analysis, declines in NLR and PSA of ≥ 90% emerged as significant independent predictors of OS and PFS. High-NLR patients who remained high or who returned to low NLR after 4 and 12 weeks showed significantly worse OS than patients with low baseline NLR. Patients with baseline Hgb > 12 g/dL had significantly longer median OS compared with patients with Hgb ≤ 12 g/dL; however, the significance of Hgb was lost at 12 weeks. Conclusions: NLR and PSA response to abiraterone was a significant predictor of OS and PFS in mCRPC patients treated with abiraterone delivered either pre- or post-chemotherapy. Furthermore, persistent increase in NLR during abiraterone has prognostic value for OS in patients with mCRPC.

Sign in / Sign up

Export Citation Format

Share Document