Real-world outcomes of advanced melanoma patients not represented in phase III trials

Michiel C. T. van Zeijl, Rawa K. Ismail, Liesbeth C. de Wreede, Alfonsus J. M. van den Eertwegh, Anthonius de Boer, Maaike van Dartel, Doranne L. Hilarius, Maureen J. B. Aarts, Franchette W. P. J. van den Berkmortel, Marye J. Boers-Sonderen, Jan-Willem B. de Groot, Geke A. P. Hospers, Ellen Kapiteijn, Djura Piersma, Rozemarijn S. van Rijn, Karijn P. M. Suijkerbuijk, Albert J. ten Tije, Astrid A. M. van der Veldt, Gerard Vreugdenhil, John B. A. G. HaanenMichel W. J. M. Wouters*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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The aim was to provide evidence on systemically treated patients with advanced melanoma not represented in phase III trials to support clinical decision-making. Analysis were performed on advanced melanoma patients diagnosed between 2014 and 2017 in the Netherlands, treated with immune- or targeted therapy, who met >= 1 trial exclusion criteria. These criteria were derived from the KEYNOTE-006 and CHECKMATE-067/-066 phase III trials. Prognostic importance of factors associated with overall survival (OS) was assessed with the Kaplan-Meier method, Cox models, predicted OS probabilities of prognostic subgroups and a conditional inference survival tree (CIST). A nationwide population-based registry was used as data source. Of 2536 systemically treated patients with advanced melanoma, 1004 (40%) patients were ineligible for phase IIII trials. Ineligible patients had a poorer median OS (mOS) compared to eligible patients (8.8 vs 23 months). Eligibility criteria strongly associated with OS in systemically treated ineligible patients were Eastern Cooperative Oncology Group Performance Score (ECOG PS) >= 2, brain metastases (BM) and lactate dehydrogenase (LDH) of >500 U/L. Patients with ECOG PS of >= 2 with or without symptomatic BM had a predicted mOS of 6.5 and 11.3 months and a 3-year survival probability of 9.3% and 23.6%, respectively. The CIST showed the strongest prognostic covariate for survival was LDH, followed by ECOG PS. The prognosis of patients with LDH of >500 U/L is poor, but long-term survival is possible. The prognosis of ineligible patients with advanced melanoma in real-world was very heterogeneous and highly dependent on LDH value, ECOG PS and symptomatic BM.

Original languageEnglish
Pages (from-to)3461-3470
Number of pages10
JournalInternational Journal of Cancer
Issue number12
Early online date4 Jul 2020
Publication statusPublished - 15 Dec 2020


  • advanced melanoma
  • decision tree
  • ineligibility
  • real-world outcomes
  • survival

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