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

Med Oncol. 2018 Jun 18;35(7):110. doi: 10.1007/s12032-018-1167-7.


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.

Keywords: Drug-related side effects and adverse reactions; Eligibility determination; Ipilimumab; Melanoma; Vemurafenib.

Publication types

  • Clinical Trial, Phase III
  • Pragmatic Clinical Trial

MeSH terms

  • Aged
  • Antineoplastic Agents, Immunological / therapeutic use
  • Canada / epidemiology
  • Cohort Studies
  • Female
  • Humans
  • Ipilimumab / therapeutic use
  • Male
  • Melanoma / diagnosis
  • Melanoma / drug therapy
  • Melanoma / epidemiology*
  • Middle Aged
  • Neoplasm Staging / methods
  • Population Surveillance* / methods
  • Retrospective Studies
  • Skin Neoplasms / diagnosis
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / epidemiology*
  • Survival Rate / trends


  • Antineoplastic Agents, Immunological
  • Ipilimumab