scholarly journals Risk factors for severe rash with use of vemurafenib alone or in combination with cobimetinib for advanced melanoma: pooled analysis of clinical trials

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ashley M. Hopkins ◽  
Akash D. Rathod ◽  
Andrew Rowland ◽  
Ganessan Kichenadasse ◽  
Michael J. Sorich
Keyword(s):  
Risk Factors ◽  
Clinical Trials ◽  
Pooled Analysis ◽  
Advanced Melanoma ◽  
Severe Rash

Abstract 5063: Cardiovascular Effects of Transdermal Testosterone in Postmenopausal Women

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
C Vitale ◽  
P Collins ◽  
G Marazzi ◽  
G Caminiti ◽  
I Lodhi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Clinical Trials ◽  
Hormone Replacement ◽  
Cardiovascular Effects ◽  
Pooled Analysis ◽  
Phase Iii ◽  
Double Blind ◽  
Treatment Groups ◽  
Clinical Program ◽  
Large Phase

Testosterone Transdermal Patch (TTP) has been developed for the treatment of postmeno-pausal women (PMW) with hypoactive sexual desire disorder (HSDD). Since the cardiovascular (CV) effects of testosterone in women are still unclear we conducted a pooled analysis of the large phase III clinical program to evaluate the efficacy and safety of 300 μg/day TTP, alone or in association with hormone replacement therapy (HRT), versus placebo in surgical or natural PMW. Design & Methods: A total of 2795 women aged between 26 –70 years (mean age 52(SD=6.8) years) were included in 5 phase III randomized, double-blind, placebo-controlled clinical trials (treatment duration range 24 – 52 weeks) as part of the TTP Clinical program. 4 studies included PMW (natural and surgical, two each respectively) receiving HRT while 1 study was conducted without HRT, in either surgical or natural PMW. Women with known CV disorders were excluded from the studies. Changes from baseline in standard metabolic and CV risk factors were compared. The incidence of stroke, myocardial infarction (MI) and venous thromboembolism (VTE) alone or as a composite CV endpoint was assessed. Results: The 2795 PMW were randomized to receive either placebo (n=1297) or TTP (n=1498). Baseline mean BMI was 27 kg/m2 (SD=5.3 kg/m2) and 56% were naturally menopausal. The demographic and baseline parameters were similar among the treatment groups. No significant changes in CV risk factors (Total Cholesterol, Triglycerides, Insulin, Glucose, Systolic and Diastolic Blood Pressure) were detected during the study period, apart from a blunting of the increases in HDL-C by TTP at 24 and 52 weeks (Placebo 52-week mean change 2.59 mg/dl vs. TTP 52-week mean change 1.20 mg/dl, p<0.005) and of the decrease in LDL-C by TTP at 24 (p<0.05), but not at 52 weeks. During the double-blind (24 weeks), placebo-controlled period of the combined studies, 4 major CV events (2 MIs and 2 strokes) were reported in placebo patients and 3 (2 MIs and 1 stroke) in those receiving TTP. One VTE occurred in a patient receiving TTP and HRT. Conclusion: TTP therapy in these clinical trials did not adversely affect CV risk profile and did not change the risk of major CV events in these surgical and naturally PMW with or without concomitant HRT.

scholarly journals Risk Models for Advanced Melanoma Patients Under Anti-PD-1 Monotherapy—Ad hoc Analyses of Pooled Data From Two Clinical Trials

2021 ◽  
Vol 11 ◽  
Author(s):  
Xue Bai ◽  
Jie Dai ◽  
Caili Li ◽  
Chuanliang Cui ◽  
Lili Mao ◽  
...  
Keyword(s):  
Risk Factors ◽  
Clinical Trials ◽  
Ad Hoc ◽  
Objective Response ◽  
Advanced Melanoma ◽  
Fold Change ◽  
Risk Models ◽  
Best Response ◽  
Melanoma Patients ◽  
Pre Treatment

Background: The best response and survival outcomes between advanced melanoma patients treated with the anti-PD-1 monotherapy vary greatly, rendering a risk model in need to optimally stratify patients based on their likelihood to benefit from the said treatment.Methods: We performed an ad hoc analysis of 89 advanced melanoma patients treated with the anti-PD-1 monotherapy from two prospective clinical trials at the Peking University Cancer Hospital from April 2016 to May 2018. Clinicodemographical characteristics, baseline and early-on-treatment (median 0.6 months after anti-PD-1 monotherapy initiation) routine laboratory variables, including complete blood count and general chemistry, and best response/survival data were extracted and analyzed in both univariate and multivariate logistic and Cox proportional hazard models.Results: After three rounds of screening, risk factors associated with a poorer PFS included a high pre-treatment neutrophil, derived neutrophil-lymphocyte ratio (dNLR), low pre-treatment hemoglobin, and low early-on-/pre-treatment fold change of eosinophil; those with a poorer OS included a high pre-treatment neutrophil, eosinophil, PLT, early-on/pre-treatment fold change of LDH and neutrophil; and those with a poorer best response included a high pre-treatment NLR and early-on-/pre-treatment LDH fold change. Risk models (scale: low, median-low, median high, and high risk) were established based on these risk factors as dichotomous variables and M stage (with vs. without distant metastasis) for PFS (HR 1.976, 95% CI, 1.507–2.592, P &lt; 0.001), OS (HR 2.348, 95% CI, 1.688–3.266), and non-responder (OR 3.586, 95% CI, 1.668–7.713, P = 0.001), respectively. For patients with low, median-low, median-high, and high risks of developing disease progression (PD), six-month PFS rates were 64.3% (95% CI, 43.5–95.0%), 37.5% (95% CI, 22.4–62.9%), 9.1% (95% CI, 3.1–26.7%), and 0%, respectively. For patients with OS risks of low, median-low, median-high, and high, OS rates at 12 months were 82.5% (95% CI, 63.1–100%), 76.6% (95% CI, 58.4–100%), 42.1% (95% CI, 26.3–67.3%), and 23.9% (95% CI, 11.1–51.3%), respectively. For patients with risks of low, median-low, median-high, and high of being a non-responder, objective response rates were 50.0% (95% CI, 15.7–84.3%), 27.8% (95% CI, 9.7–53.5%), 10.3% (95% CI, 2.9–24.2%), and 0%, respectively.Conclusion: A risk scoring model based on the clinicodemographical characteristics and easily obtainable routinely tested laboratory biomarkers may facilitate the best response and survival outcome prediction and personalized therapeutic decision making for the anti-PD-1 monotherapy treated advanced melanoma patients in Asia.

Controlling Hypertension and Stroke Prevention – From Guideline to Clinical Practice

2011 ◽  
Vol 3 (1) ◽  
pp. 30
Author(s):  
Anding Xu ◽  
Zefeng Tan ◽  
◽  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Clinical Trials ◽  
Clinical Practice ◽  
Stroke Prevention ◽  
Modifiable Risk Factors ◽  
Cerebrovascular Events

Hypertension is the most important of the prevalent and modifiable risk factors for stroke. Based on evidence, blood pressure (BP) lowering is recommended in guidelines for the prevention of stroke. However, there are still some uncertainties in the guidelines for controlling BP and preventing stroke in patients with previous cerebrovascular events, such as the goal BP, who to treat and which class of BP-lowering drugs to use. This article discusses these questions by reviewing guidelines and corresponding clinical trials, with the aim of reducing the gap between guidelines and clinical practice.

scholarly journals Novel immune checkpoints beyond PD-1 in advanced melanoma

2021 ◽  
Author(s):  
Nina Zila ◽  
Christoph Hoeller ◽  
Verena Paulitschke
Keyword(s):  
Clinical Trials ◽  
Checkpoint Inhibitors ◽  
Short Review ◽  
Therapy Resistance ◽  
Advanced Melanoma ◽  
Immune Checkpoints ◽  
Malignant Diseases ◽  
Foreseeable Future ◽  
Cell Responses ◽  
Therapeutic Landscape

SummaryIn malignant diseases, targeting of immune checkpoints successfully changed the therapeutic landscape and helped to unleash anti-tumor T cell responses, resulting in durable clinical outcomes, but only in up to 50% of patients. The success of these therapies and the need to overcome intrinsic and acquired therapy resistance stimulated research to identify new pathways and targets. Numerous clinical trials are currently evaluating novel checkpoint inhibitors or recently developed strategies like modulating the tumor microenvironment, mostly in combination with approved therapies. This short review briefly discusses promising therapeutic targets, currently still under investigation, with the chance to realize clinical application in the foreseeable future.

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