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Generalizability of clinical trials of advanced melanoma in the real-world, population-based setting

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Abstract

Results from novel therapeutics trials are not always generalizable to real-world patients. We aimed to determine the pattern in which trial findings are applied in a population-based setting of melanoma patients and consequent treatment outcomes. Patients with unresectable disease during 2011–2014 and referred to cancer centers in a large Canadian province were retrospectively reviewed. Based on eligibility criteria as described in registration trials of vemurafenib (Vem) and ipilimumab (Ipi), we classified patients into trial-eligible and ineligible and those treated and untreated with these agents. We identified 290 patients with known BRAF status for the Vem analysis and 212 patients previously treated with first-line agents for the Ipi analysis. For the Vem cohort, a total of 49 patients were considered trial-eligible, of whom 36 (73%) received treatment. For the Ipi cohort, there were 119 trial-eligible cases of whom 43 (36%) received therapy. Factors other than eligibility criteria most frequently associated with non-treatment in these cohorts included concerns regarding treatment harm and patient preferences. In multivariable analysis, overall survival was improved in Vem cohort patients considered trial-eligible and treated compared to those who were ineligible. Within the Ipi cohort, survival was improved in trial-eligible patients regardless of whether they received Ipi compared to ineligible patients. Real-world uptake of new melanoma treatments was suboptimal, and non-use in trial-eligible patients was frequent. Future clinical trials that are more pragmatically designed to include participants who better reflect the real-world population may facilitate increased uptake of novel therapeutics into routine clinical practice.

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Funding

This study was funded by a student grant from the Mach-Gaensslen Foundation of Canada.

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Authors and Affiliations

  1. Department of Medicine, University of Calgary, 3330 Hospital Dr NW, Calgary, AB, T2N 4N1, Canada

    Davis Sam

  2. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD, 21205, USA

    Gillian Gresham

  3. Department of Clinical Oncology, Faculty of Medicine, Ain Shams University, Abbaseyya, 1156, Cairo, Egypt

    Omar Abdel-Rahman

  4. Department of Oncology, Tom Baker Cancer Center, 1331 29 St NW, Calgary, AB, T2N 4N2, Canada

    Winson Y. Cheung

Authors
  1. Davis Sam
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  2. Gillian Gresham
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  3. Omar Abdel-Rahman
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  4. Winson Y. Cheung
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Corresponding author

Correspondence to Winson Y. Cheung.

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The authors declare that they have no conflict of interest.

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Sam, D., Gresham, G., Abdel-Rahman, O. et al. Generalizability of clinical trials of advanced melanoma in the real-world, population-based setting. Med Oncol 35, 110 (2018). https://doi.org/10.1007/s12032-018-1167-7

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  • DOI: https://doi.org/10.1007/s12032-018-1167-7

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