A population-based study of the treatment effect of first-line ipilimumab for metastatic or unresectable melanoma

Ipilimumab is an anti-CTLA4 monoclonal antibody with demonstrated efficacy for metastatic melanoma in randomized controlled trials, including in the first-line setting. Population-based outcomes directly compared with historic chemotherapy treatment in metastatic or unresectable melanoma are lacking. Using population-based data from the province of Ontario, the benefit of first-line ipilimumab was estimated by comparing outcomes of patients treated with first-line dacarbazine over the period 2007–2009 with patients treated over the period 2010–2015 with first-line ipilimumab. Cutaneous and noncutaneous cases were included. The administrative data set utilized was high-dimensional; meaning, there was a large number of variables relative to the sample size. To adjust for important confounders among the many available variables, we utilized a double-selection method, a modified machine learning algorithm to extract the important variables that were related to both survival times and treatment usage. Time-dependent treatment modeling was utilized. Among the 2793 melanoma patients receiving palliative treatment (systemic therapy, surgery, or radiation) in Ontario (2007–2015), there were 289 patients treated with first-line ipilimumab (2010–2015) and 175 patients treated with first-line dacarbazine (2007–2009). For first-line ipilimumab, the adjusted hazard ratio compared with dacarbazine for overall survival (OS) was 0.63 (95% confidence interval: 0.47–0.84) with a 1-year survival of 46.5 versus 18.9% with dacarbazine. In subgroup analysis, ipilimumab was associated with improved OS across groups (age, sex, comorbidity, income quintile, previous interferon). First-line ipilimumab was found to have a significant OS benefit compared with historical controls in a population including those patients not routinely included in clinical trials. The treatment effect was similar to randomized controlled trials, suggesting a meaningful benefit when utilized in a population-based setting. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. https://ift.tt/1hexVwJ Correspondence to Timothy Hanna, MD, MSc, PhD, FRCPC, Division of Cancer Care and Epidemiology, Cancer Research Institute, Queen's University, 10 Stuart Street, 2nd Level, Kingston, ON, Canada K7L3N6 Tel: +1 613 533 6895; fax: +1 613 533 6794; e-mail: tim.hanna@kingstonhsc.ca Received August 29, 2018 Accepted January 13, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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