Age influence on adverse events in patients treated with abiraterone plus prednisone, enzalutamide and radium223 for metastatic castration resistant prostate cancer: Analysis of real life data from Eudra Vigilance database

Background: To assess the efficacy and safety of treatment with abiraterone acetate (AA) in chemotherapy-naïve men with metastatic castration-resistant prostate cancer (mCRPC) in the ‘real-life’ setting. Methods: Data acquisition on the outcomes of the use of AA in chemotherapy-naive patients with mCRPC was performed by a MEDLINE comprehensive systematic literature search using combinations of the following key words: ‘prostate cancer’, ‘metastatic’, ‘castration resistant’, ‘abiraterone’, ‘real life’, and excluding controlled clinical trials (phase II and III studies). Identification and selection of the studies was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria. Outcomes of interest were overall survival (OS), progression-free survival (PFS), 12-week 50% reduction in prostate-specific antigen (PSA), and grade 3 and higher adverse events. Data were narratively synthesized in light of methodological and clinical heterogeneity. Results: Within the eight identified studies that fulfilled the criteria, a total of 801 patients were included in the meta-analysis. Baseline PSA ranged between 9.5 and 212.0 ng/ml. Most of the patients had bone metastases. Duration of treatment with AA was longer in the studies with lower baseline PSA levels. The median OS ranged between 14 and 36.4 months. The PFS, assessed according to different definitions, ranged from 3.9 to 18.5 months. A 50% PSA reduction at 12 weeks was reached by a variable percentage of patients ranging from 36.0% to 62.1%. Finally, the rate of grade 3 and higher adverse events was reported in three studies and ranged from 4.4% to 15.5%. Conclusions: Despite the high grade of heterogeneity among studies, treatment with AA seems to ensure good survival outcomes in the ‘real-life’ setting. However, prospective studies based on patients’ characteristics being more similar to ‘real-life’ patients are necessary.

Download Full-text

Overall and progression-free survival with cabazitaxel in metastatic castration-resistant prostate cancer in routine clinical practice: the FUJI cohort

British Journal of Cancer ◽

10.1038/s41416-019-0611-6 ◽

2019 ◽

Vol 121 (12) ◽

pp. 1001-1008 ◽

Cited By ~ 9

Author(s):

Magali Rouyer ◽

◽

Stéphane Oudard ◽

Florence Joly ◽

Karim Fizazi ◽

...

Keyword(s):

Prostate Cancer ◽

Adverse Events ◽

Real Life ◽

Progression Free Survival ◽

European Medicines Agency ◽

Castration Resistant Prostate Cancer ◽

Free Survival ◽

Castration Resistant ◽

Grade 3 ◽

Metastatic Sites

Abstract Background Cabazitaxel is a treatment of metastatic castration-resistant prostate cancer (mCRPC) after docetaxel failure. The FUJI cohort aimed to confirm the real-life overall and progression-free survival (OS, PFS) and safety of cabazitaxel. Methods Multicentre, non-interventional cohort of French mCRPC patients initiating cabazitaxel between 2013 and 2015, followed 18 months. Results Four hundred one patients were recruited in 42 centres. At inclusion, median age was 70, main metastatic sites were bones (87%), lymph nodes (42%) and visceral (20%). 18% had cabazitaxel in 2nd-line treatment, 39% in 3rd-line and 43% in 4th-line or beyond. All had prior docetaxel, and 82% prior abiraterone, enzalutamide or both. Median duration of cabazitaxel treatment was 3.4 months. Median OS from cabazitaxel initiation was 11.9 months [95% CI: 10.1–12.9]. In multivariate analyses, grade ≥ 3 adverse events, visceral metastases, polymedication, and >5 bone metastases were associated with a shorter OS. Main grade ≥ 3 adverse events were haematological with 8% febrile neutropenia. Conclusion Real-life survival with cabazitaxel in FUJI was shorter than in TROPIC (pivotal trial, median OS 15.1 months) or PROSELICA (clinical trial 20 vs 25 mg/m2, median OS, respectively, 13.4 and 14.5 months). There was no effect of treatment-line on survival. No unexpected adverse concerns were identified. Study registration It was registered with the European Medicines Agency EUPASS registry, available at www.encepp.eu, as EUPAS10391. It has been approved as an ENCEPP SEAL study.

Download Full-text

Adverse events related to different antimuscarinics and beta-3-agonist: Analysis of real-life data from Eudra-Vigilance

European Urology ◽

10.1016/s0302-2838(21)00411-5 ◽

2021 ◽

Vol 79 ◽

pp. S21-S22

Author(s):

C. De Nunzio ◽

A. Nacchia ◽

R. Lombardo ◽

A. Franco ◽

G. Tema ◽

...

Keyword(s):

Adverse Events ◽

Real Life ◽

Life Data ◽

Real Life Data

Download Full-text

Weekly low-dose docetaxel is an effective treatment with fewer adverse events for metastatic castration-resistant prostate cancer in Taiwanese patients

Urological Science ◽

10.1016/j.urols.2015.07.011 ◽

2015 ◽

Vol 26 (4) ◽

pp. 267-270 ◽

Cited By ~ 2

Author(s):

Cheng-Li Kao ◽

Tai-Lung Cha ◽

Chien-Chang Kao ◽

Chu-Wei Tsao ◽

Shou-Hung Tang ◽

...

Keyword(s):

Prostate Cancer ◽

Adverse Events ◽

Effective Treatment ◽

Low Dose ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant

Download Full-text

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

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-002919 ◽

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.

Download Full-text