Real-World Outcomes in First-Line Treatment of Metastatic Castration-Resistant Prostate Cancer : The Prostate Cancer Registry

Altres ajuts: This study was funded by Janssen EMEA. Janssen EMEA contributed to the study design, the collection, analysis, and interpretation of data, the writing of the report, and the decision to submit the paper for publication.Metastatic prostate cancer has a 30% 5-year survival rate despite recent therapeutic advances. There is a need to improve the clinical understanding and treatment of this disease, particularly in the real-world setting and among patients who are under-represented in clinical trials. We aimed to evaluate the characteristics and clinical outcomes of patients who received their first treatment for metastatic castration-resistant prostate cancer (mCRPC) in routine clinical practice, independent of treatment used, including subgroups with baseline cardiac disease, diabetes mellitus, or visceral metastases. Prospective, noninterventional analysis of patient record data in the multicenter Prostate Cancer Registry (PCR) of men with mCRPC. The data were collected in 16 countries with the aim of recruiting more than 3000 patients between 2013 and 2016. The study end date was 9 July 2018. Data evaluated included baseline characteristics, treatment exposure, and efficacy outcomes [overall survival (OS) and time to progression (TTP)] of patients treated with abiraterone acetate plus prednisone or prednisolone (collectively, "abiraterone"), enzalutamide, or docetaxel. Descriptive outcomes are reported from the overall patient population and subgroups of patients with baseline cardiovascular disease, diabetes mellitus, or visceral metastases. The treatment effects for time to progression were compared for the overall patient population. The study enrollment period lasted 2.5 years, and each patient was followed for a maximum of 3 years. A total of 1874 patients in the PCR had not received previous mCRPC treatment at baseline, although they had received androgen-deprivation therapy. Prevalent co-morbidities included cardiovascular disease in 65.4% and diabetes mellitus in 17.4% of patients. Baseline characteristics suggested that patients with more advanced disease received docetaxel treatment. In the overall patient population, the median time to progression with abiraterone, enzalutamide, and docetaxel as first-line mCRPC therapy was 9.6, 10.3, and 7.6 months, respectively, and median OS was 27.1, 27.1, and 27.9 months, respectively. Outcomes in the subgroups of patients with cardiovascular disease or diabetes mellitus were similar to those of the whole population in the analysis. As expected, patients with visceral metastases had shorter TTP and OS than patients in the overall population. This analysis shows, for the first time, the effectiveness in parallel of first-line abiraterone, enzalutamide, and docetaxel in mCRPC, including in patients with co-morbidities such as cardiovascular disease or diabetes mellitus or in patients with visceral metastases. These real-world findings from the PCR provide meaningful information to help manage mCRPC, particularly in patients under-represented in clinical studies. ClinicalTrials.gov identifier NCT02236637; registered September 2014. The online version of this article (10.1007/s11523-020-00720-2) contains supplementary material, which is available to authorized users

LocoMMotion:a prospective, non-interventional, multinational study of real-life current standards of care in patients with relapsed and/or refractory multiple myeloma

Despite treatment advances, patients with multiple myeloma (MM) often progress through standard drug classes including proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 monoclonal antibodies (mAbs). LocoMMotion (ClinicalTrials.gov identifier: NCT04035226) is the first prospective study of real-life standard of care (SOC) in triple-class exposed (received at least a PI, IMiD, and anti-CD38 mAb) patients with relapsed/refractory MM (RRMM). Patients (N = 248; ECOG performance status of 0–1, ≥3 prior lines of therapy or double refractory to a PI and IMiD) were treated with median 4.0 (range, 1–20) cycles of SOC therapy. Overall response rate was 29.8% (95% CI: 24.2–36.0). Median progression-free survival (PFS) and median overall survival (OS) were 4.6 (95% CI: 3.9–5.6) and 12.4 months (95% CI: 10.3–NE). Treatment-emergent adverse events (TEAEs) were reported in 83.5% of patients (52.8% grade 3/4). Altogether, 107 deaths occurred, due to progressive disease (n = 74), TEAEs (n = 19), and other reasons (n = 14). The 92 varied regimens utilized demonstrate a lack of clear SOC for heavily pretreated, triple-class exposed patients with RRMM in real-world practice and result in poor outcomes. This supports a need for new treatments with novel mechanisms of action

Pharmacotherapy of disruptive behavior and item changes on a standardized rating scale: pooled analysis of risperidone effects in children with subaverage IQ.

Contains fulltext : 49128.pdf (publisher's version ) (Open Access)BACKGROUND: Disruptive behavior disorders (DBDs), excluding attention deficit/hyperactivity disorder (ADHD), are characterized by a repetitive pattern of antisocial, aggressive, and defiant behavior involving major violations of age-appropriate norms, resulting in significant functional impairment. Risperidone is licensed for the treatment of DBDs in children, adolescents, and adults in several countries. The aim of this study was to determine the effect of risperidone in a clinical setting on the symptom items of the Nisonger Child Behavior Rating Form (N-CBRF), used for the assessment of DBD patients. METHOD: Data from two 6-week, randomized, double-blind, placebo-controlled trials of risperidone oral solution (0.02-0.06 mg/kg/day) in children with DBDs and subaverage IQ (mild, moderate mental retardation and borderline IQ) were pooled for analysis. RESULTS: Risperidone produced improvement in both the Social Competence and the Problem Behavior N-CBRF subscales. Risperidone reduced symptoms in the Problem Behavior subscales (e.g., Conduct Problem, Insecure/Anxious) but also improved positive behaviors on the Social Competence subscales. Unlike most problem-behavior items, certain items reflecting "Affective insecurity" (e.g., shy, timid; clings to adults; crying, tearful episodes) failed to improve. This was also true of social disinterest and certain rituals. No items showed any worsening of symptoms with active medication. CONCLUSION: Whereas most categories of problem behavior improved with risperidone, items reflecting "affective insecurity" and some infrequently endorsed items were unaffected in these children with DBDs and subaverage IQ. These data may provide a more refined knowledge of risperidone's therapeutic effects in such children

Guselkumab-Treated Patients with Plaque Psoriasis Who Achieved Complete Skin Clearance for ≥ 156 Consecutive Weeks : A Post-Hoc Analysis From the VOYAGE 1 Clinical Trial

Treatment of moderate-to-severe plaque psoriasis with biologics, such as guselkumab, has demonstrated greater efficacy over traditional non-biologic treatments. However, given patient diversity, greater understanding of the relationship between patient characteristics, positive clinical outcomes, and long-term response to biologics is crucial for optimizing treatment choices. This post-hoc analysis of the 5-year VOYAGE 1 clinical trial compares baseline characteristics of patients maintaining a Psoriasis Area and Severity Index (PASI) score of 0 at all visits for ≥ 156 consecutive weeks (PASI = 0 group) with those that never achieve PASI = 0 (comparator group), using descriptive statistics and a multiple logistic regression model. Guselkumab plasma trough concentrations in both response groups were assessed from Weeks 4-156. Of patients who started guselkumab treatment at Week 0 or at Week 16 after switching from placebo, 22.7% (112/494) maintained PASI = 0 for ≥ 156 consecutive weeks. Numerical differences in baseline characteristics, including age, obesity, diabetes, PASI score, disease duration, smoking status, and psoriatic arthritis comorbidity, were identified between the PASI = 0 group and comparator group. Plasma guselkumab levels were consistently higher in the PASI = 0 group. Multiple logistic regression analysis revealed absence of diabetes, lower Dermatology Life Quality Index score at baseline, and higher Week 4 guselkumab plasma concentration as significantly (p < 0.05) associated with the PASI = 0 group. A substantial (22.7%) number of guselkumab-treated patients in the VOYAGE 1 clinical trial maintained complete skin clearance for a consecutive period of ≥ 156 weeks. Factors associated with this outcome may suggest clinical benefits of holistic treatment approaches. NCT02207231

Matrix Approach of Seismic Imaging: Application to the Erebus Volcano, Antarctica

International audienc

Real-World Safety and Efficacy Outcomes with Abiraterone Acetate Plus Prednisone or Prednisolone as the First- or Second-Line Treatment for Metastatic Castration-Resistant Prostate Cancer : Data from the Prostate Cancer Registry

Despite standard-of-care androgen-deprivation therapy and an increasing number of treatment options, the mortality rate for prostate cancer remains high. Progress to metastatic castration-resistant prostate cancer (mCRPC) necessitates additional treatments. Abiraterone acetate plus prednisone or prednisolone (AAP) prolongs survival in chemotherapy-naive and docetaxel-experienced patients. To evaluate the real-world safety and efficacy of AAP as first-line and second-line [post-docetaxel only (AAP-PD)] treatment in patients with mCRPC. The Prostate Cancer Registry (PCR) was a prospective, international, observational study of patients with mCRPC in routine clinical practice. Men aged ≥ 18 years with confirmed mCRPC were included. Baseline characteristics, safety (treatment-emergent adverse events, treatment-emergent severe adverse events), and efficacy [progression-free survival (PFS) and overall survival (OS)] were analyzed. At baseline, patients who received first-line AAP (n = 754) were generally older than patients who received AAP-PD (n = 354); median age was 76 years and 70 years, respectively. However, the rate of visceral metastasis was higher in the AAP-PD cohort than in the AAP cohort (17.7% vs. 9.6%, respectively). Demographics and disease characteristics of patients with baseline cardiovascular disease were similar to those of the overall registry population. Efficacy outcomes were similar for all patients, regardless of the line of AAP therapy. For first-line AAP and AAP-PD, respectively, the median PFS was 8.9 and 5.8 months for all patients and 9.1 and 6.0 months for patients with cardiovascular comorbidities; median OS was 27.1 and 23.4 months for all patients, and 27.4 and 23.1 months for patients with cardiovascular comorbidities. There were no unexpected adverse events in any patient subgroup. These real-world data complement the findings from randomized controlled trials, indicating that first- and second-line AAP is well tolerated and effective in patients with mCRPC, including those with underlying CV comorbidities. NCT02236637, registered 8 September 2014. The online version contains supplementary material available at 10.1007/s11523-021-00807-4

Real-World Outcomes in First-Line Treatment of Metastatic Castration-Resistant Prostate Cancer : The Prostate Cancer Registry

Altres ajuts: This study was funded by Janssen EMEA. Janssen EMEA contributed to the study design, the collection, analysis, and interpretation of data, the writing of the report, and the decision to submit the paper for publication.Metastatic prostate cancer has a 30% 5-year survival rate despite recent therapeutic advances. There is a need to improve the clinical understanding and treatment of this disease, particularly in the real-world setting and among patients who are under-represented in clinical trials. We aimed to evaluate the characteristics and clinical outcomes of patients who received their first treatment for metastatic castration-resistant prostate cancer (mCRPC) in routine clinical practice, independent of treatment used, including subgroups with baseline cardiac disease, diabetes mellitus, or visceral metastases. Prospective, noninterventional analysis of patient record data in the multicenter Prostate Cancer Registry (PCR) of men with mCRPC. The data were collected in 16 countries with the aim of recruiting more than 3000 patients between 2013 and 2016. The study end date was 9 July 2018. Data evaluated included baseline characteristics, treatment exposure, and efficacy outcomes [overall survival (OS) and time to progression (TTP)] of patients treated with abiraterone acetate plus prednisone or prednisolone (collectively, "abiraterone"), enzalutamide, or docetaxel. Descriptive outcomes are reported from the overall patient population and subgroups of patients with baseline cardiovascular disease, diabetes mellitus, or visceral metastases. The treatment effects for time to progression were compared for the overall patient population. The study enrollment period lasted 2.5 years, and each patient was followed for a maximum of 3 years. A total of 1874 patients in the PCR had not received previous mCRPC treatment at baseline, although they had received androgen-deprivation therapy. Prevalent co-morbidities included cardiovascular disease in 65.4% and diabetes mellitus in 17.4% of patients. Baseline characteristics suggested that patients with more advanced disease received docetaxel treatment. In the overall patient population, the median time to progression with abiraterone, enzalutamide, and docetaxel as first-line mCRPC therapy was 9.6, 10.3, and 7.6 months, respectively, and median OS was 27.1, 27.1, and 27.9 months, respectively. Outcomes in the subgroups of patients with cardiovascular disease or diabetes mellitus were similar to those of the whole population in the analysis. As expected, patients with visceral metastases had shorter TTP and OS than patients in the overall population. This analysis shows, for the first time, the effectiveness in parallel of first-line abiraterone, enzalutamide, and docetaxel in mCRPC, including in patients with co-morbidities such as cardiovascular disease or diabetes mellitus or in patients with visceral metastases. These real-world findings from the PCR provide meaningful information to help manage mCRPC, particularly in patients under-represented in clinical studies. ClinicalTrials.gov identifier NCT02236637; registered September 2014. The online version of this article (10.1007/s11523-020-00720-2) contains supplementary material, which is available to authorized users