OBJECTIVES Systemic palliative treatment and patient population characteristics in the real-world settings, most likely differ from the controlled trial setting used to inform regulatory and reimbursement decisions. Hence outcomes could consequently deviate. The aim of this research was to examine the potential between trial and real-world difference in patient populations and the treatment with the immunotherapies (e.g. nivolumab, ipilimumab and pembrolizumab) in melanoma stage III-IV patients with wild-type BRAF600 mutation.

METHODS : Firstly, a literature review was conducted to gather Dutch regulatory and reimbursement reports for immunotherapy treatments. The present therapeutic indications as well as patient inclusion and exclusion criteria were compared versus treatment and population data from the existing trials. Secondly, individual hospital patient files, from melanoma stage III-IV patients between 2013 and 2019 were screened and analyzed by two independent researchers in order to quantitatively compare patient baseline characteristics and survival outcomes between the trial setting and clinical melanoma practice in the Netherlands. This also involved specific interpretation and confirmation of grade III-IV adverse events.

RESULTS It was found that the definition of melanoma stage III-IV, the handling the patient criteria as well as therapeutic indications were comparable in the clinical as in the real-world setting. A preliminary data analysis turned out that patients in a real-world versus trial setting generally start their treatment with a higher performance status after diagnosis. Additionally, adverse events classified grade III-IV, are more frequent for the more heterogenic real-world melanoma patient population.

CONCLUSIONS Patient performance score and more frequently occurrence of grade III-IV adverse events for patients with melanoma stage III-IV in real-life, could result in a lower Quality of Life, worser prognosis and higher healthcare costs. Hence, further cost-effectiveness analyses for the active substances nivolumab, ipilimumab and pembrolizumab will be re-considered using data obtained in the real-world.