Estimating Long-Term Survivorship Rates Among Patients With Resected Stage III/IV Melanoma: Analyses From CheckMate 238 and European Organization for Research and Treatment of Cancer 18071 Trials.

Purpose: Standard-of-care treatments for patients with resected stage III/IV melanoma include the immuno-oncology (IO) agents nivolumab (NIVO) and ipilimumab (IPI). This study used mixture cure models (MCMs) to estimate cure rates among patients treated with NIVO or IPI in the phase III CheckMate 238 (ClinicalTrials.gov identifier: NCT02388906) and European Organization for Research and Treatment of Cancer (EORTC) 18071 (ClinicalTrials.

Administering selected subscales of patient-reported outcome questionnaires to reduce patient burden and increase relevance: a position statement on a modular approach.

Patient-reported outcome (PRO) questionnaires considered in this paper contain multiple subscales, although not all subscales are equally relevant for administration in all target patient populations. A group of measurement experts, developers, license holders, and other scientific-, regulatory-, payer-, and patient-focused stakeholders participated in a panel to discuss the benefits and challenges of a modular approach, defined here as administering a subset of subscales out of a multi-scaled PRO measure. This paper supports the position that it is acceptable, and sometimes preferable, to take a modular approach when administering PRO questionnaires, provided that certain conditions have been met and a rigorous selection process performed.

Cost-Utility of Nivolumab Plus Ipilimumab in First-Line Treatment of Advanced Melanoma in the United States: An Analysis Using Long-Term Overall Survival Data from Checkmate 067.

Objective: The aim of this study was to evaluate the cost-utility of nivolumab plus ipilimumab (NIVO + IPI) versus other first-line therapies for advanced melanoma in the United States (US) from the third-party payer perspective.

Methods: This analysis estimated total expected life-years (LYs), quality-adjusted LYs (QALYs), and costs for first-line treatments of advanced melanoma during a 30-year time horizon using indirect treatment comparisons based on time-varying hazard ratios (HRs) and a three-state partitioned survival model. Overall survival (OS) and progression-free survival reference curves were extrapolated based on 5-year follow-up from the phase III Checkmate 067 trial (NCT01844505).

Real-World nivolumab dosing patterns and safety outcomes in patients receiving adjuvant therapy for melanoma.

Background: Nivolumab at a dose of 480 mg every 4 weeks (Q4W) is approved for the adjuvant treatment of melanoma. However, real-world data on this regimen are limited in this setting.

Methods: This retrospective observational study utilized data from the US Oncology Network iKnowMed electronic health record database and patient medical charts.

Heterogeneity in Survival with Immune Checkpoint Inhibitors and Its Implications for Survival Extrapolations: A Case Study in Advanced Melanoma.

Background: Survival heterogeneity and limited trial follow-up present challenges for estimating lifetime benefits of oncology therapies. This study used CheckMate 067 (NCT01844505) extended follow-up data to assess the predictive accuracy of standard parametric and flexible models in estimating the long-term overall survival benefit of nivolumab plus ipilimumab (an immune checkpoint inhibitor combination) in advanced melanoma.

Methods: Six sets of survival models (standard parametric, piecewise, cubic spline, mixture cure, parametric mixture, and landmark response models) were independently fitted to overall survival data for treatments in CheckMate 067 (nivolumab plus ipilimumab, nivolumab, and ipilimumab) using successive data cuts (28, 40, 52, and 60 mo).

Overall survival in the real-world and clinical trials: a case study validating external controls in advanced melanoma.

We assessed the suitability of real-world data (RWD) as an external control for analysis of overall survival (OS) compared with clinical trial data (CTD) in advanced melanoma. OS among adults receiving ipilimumab for advanced melanoma was compared between trials (CTD group) and the Flatiron Health database (RWD group) using Cox models. Adjusted analyses accounted for differences in baseline factors; missing data were addressed through multiple imputation.

Treatment-free survival over extended follow-up of patients with advanced melanoma treated with immune checkpoint inhibitors in CheckMate 067.

Background: Treatment-free survival (TFS) characterizes disease control after discontinuation of immune checkpoint inhibitors (ICIs) until subsequent therapy or death. We previously evaluated TFS in a pooled analysis of the CheckMate 067 and CheckMate 069 trials of the ICIs nivolumab and ipilimumab, alone or in combination, in patients with advanced melanoma after minimum follow-up of 36 months. This analysis investigated TFS differences between treatments in CheckMate 067 after a minimum follow-up of 60 months, and their relation to overall survival (OS) differences.

Indirect treatment comparison of nivolumab versus placebo as adjuvant treatment for resected melanoma.

Background: Nivolumab (an anti-programmed death-1 antibody) is an adjuvant standard of care for patients with high-risk resected melanoma, although a watch-and-wait strategy remains an option. In the absence of head-to-head evidence, an indirect treatment comparison (ITC) of adjuvant nivolumab versus placebo, the proxy for a watch-and-wait strategy, was conducted in patients with high-risk resected melanoma.

Methods: An ITC using the Bucher method compared nivolumab with placebo using intention-to-treat population data from the phase III CheckMate 238 (nivolumab vs ipilimumab; minimum follow-up, 4 years; NCT02388906) and European Organisation for Research and Treatment of Cancer (EORTC) 18071 (ipilimumab vs placebo; minimum follow-up, ≈4.

Long-term real-world experience with ipilimumab and non-ipilimumab therapies in advanced melanoma: the IMAGE study.

Background: Ipilimumab has shown long-term overall survival (OS) in patients with advanced melanoma in clinical trials, but robust real-world evidence is lacking. We present long-term outcomes from the IMAGE study (NCT01511913) in patients receiving ipilimumab and/or non-ipilimumab (any approved treatment other than ipilimumab) systemic therapies.

Methods: IMAGE was a multinational, prospective, observational study assessing adult patients with advanced melanoma treated with ipilimumab or non-ipilimumab systemic therapies between June 2012 and March 2015 with ≥3 years of follow-up.

Comparative efficacy and safety of adjuvant nivolumab versus other treatments in adults with resected melanoma: a systematic literature review and network meta-analysis.

Background: Immune checkpoint inhibitors and targeted therapies are approved for adjuvant treatment of patients with resected melanoma; however, they have not been compared in randomized controlled trials (RCTs). We compared the efficacy and safety of adjuvant nivolumab with other approved treatments using available evidence from RCTs in a Bayesian network meta-analysis (NMA).

Methods: A systematic literature review was conducted through May 2019 to identify relevant RCTs evaluating approved adjuvant treatments.

Cost-Utility Analysis of Nivolumab in Adjuvant Treatment of Melanoma in France.

Introduction: The aim of the current study is to estimate the cost-effectiveness of adjuvant treatment with nivolumab relative to clinically relevant comparators in adult patients with melanoma with lymph node involvement or metastatic disease who have undergone complete resection from a French societal perspective.

Methods: The comparators were observation, low-dose interferon and pembrolizumab. A subgroup analysis was carried out in patients with BRAF mutation, adding dabrafenib plus trametinib.

Evaluating the potential of relapse-free survival as a surrogate for overall survival in the adjuvant therapy of melanoma with checkpoint inhibitors.

Introduction: Recent changes in the adjuvant treatment of melanoma have raised interest in confirming relapse-free survival (RFS) as a surrogate for overall survival (OS).

Methods: We explore this issue with the meta-analytic framework, using individual patient data from the European Organisation for Research and Treatment of Cancer (EORTC) 18071 trial of ipilimumab and published results from other adjuvant trials.

Results: The individual patient data analysis results at a median follow-up of 5.

Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma.

Background: Nivolumab plus ipilimumab or nivolumab alone resulted in longer progression-free and overall survival than ipilimumab alone in a trial involving patients with advanced melanoma. We now report 5-year outcomes in the trial.

Methods: We randomly assigned patients with previously untreated advanced melanoma to receive one of the following regimens: nivolumab (at a dose of 1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram every 2 weeks); nivolumab (3 mg per kilogram every 2 weeks) plus ipilimumab-matched placebo; or ipilimumab (3 mg per kilogram every 3 weeks for four doses) plus nivolumab-matched placebo.

Healthcare cost comparison analysis of nivolumab in combination with ipilimumab versus nivolumab monotherapy and ipilimumab monotherapy in advanced melanoma.

Background: Monoclonal antibodies targeting the cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) (e.g., ipilimumab [IPI]) and the programmed cell death-1 (PD1) receptor (e.

Clinical and economic benefits of extended treatment with apixaban for the treatment and prevention of recurrent venous thromboembolism in Canada.

Background and objective Venous thromboembolism (VTE) is associated with long-term clinical and economic burden. Clinical guidelines generally recommend at least 3 months of anticoagulation, but, in clinical practice, concerns over bleeding risk often limit extended treatment. Apixaban was studied for extended VTE treatment in the AMPLIFY-EXT trial, demonstrating superiority to placebo in VTE reduction without increasing risk of major bleeding.

Depression and mortality in the visually-impaired, community-dwelling, elderly population of Quebec.

Purpose: To assess the effect of visual impairment (VI) on the risk of depression or death in the community-dwelling elderly population.

Methods: A population-based, retrospective fixed cohort study was conducted in the community-dwelling elderly (age > or = 65 years) outpatient population of Quebec. The cohort was assembled through the Quebec medical services database and consisted of the 5063 patients aged > or = 65 years who received a diagnosis of VI during the years 2000-2004.

Integrating feedback from a clinical data warehouse into practice organisation.

A patient oriented hospital information system (ARIANE) was inaugurated at the Sherbrooke University hospital (CHUS) in 1990 and a clinical data warehouse (CDW) completed 2004. The CDW is updated from ARIANE every 24h and includes ICD discharge diagnosis data, visit DRG and SNOMED encoding. The data is encrypted on storage.

When is bioavailable testosterone a redundant test in the diagnosis of hypogonadism in men?

Objectives: Total testosterone (TT) is frequently prescribed with an SHBG and/or free or bioavailable testosterone measurement. Our objective was to identify a TT range for which subsequent SHBG measurement/calculation adds no additional clinical information.

Design And Methods: Study data were composed of 3955 sets of TT, SHBG and calculated bioavailable testosterone (cBAT) results from unscreened ambulatory male subjects, aged 18-99.