Pharmacogenetics and cost-effectiveness of systemic treatment in soft tissue sarcoma

Verboom, M.C. (2019)

Doctoral Thesis

This thesis on systemic treatment options in soft tissue sarcomas consists of two parts. In part I, the pharmacogenetics of systemic gastro-intestinal stromal tumors (GIST) treatment is investigated. SNPs related to the pharmacokinetics and pharmacodynamics of imatinib and sunitinib have been associated to survival and to toxicity. SNPs in VEGFA and SLCO1B3 have been associated to worse progression free survival during imatinib treatment of advanced GIST. SNPs in ABCG2 and CYP1A2 have been associated with the need for dose reduction in patients receiving imatinib for GIST. A SNP in POR was associated with better progression free survival during sunitinib treatment of advanced GIST . In part II the usage of trabectedin is soft tissue sarcomas (STS) in the Netherlands is studied. Trabectedin as second line treatment of soft tissue sarcoma was compared to ifosfamide monotherapy. The Incremental Cost-Effectiveness Ratio for leiomyosarcomas and liposarcomas was at the top end of what is considered acceptable in the Netherlands. For other soft tissue sarcomas subtypes, ifosfamide dominated trabectedin. The venous access related adverse events of trabectedin have been described. The research in this thesis contributes towards personalised treatment for advanced soft tissue sarcomas.

• Pharmacogenetics
• Imatinib
• Sunitinib
• Trabectedin
• Gastro-Intestial Stromal Tumor
• Soft tissue sarcoma
• Cost-effectiveness
• GIST

• All authors: Verboom, M.C.
• Supervisor: Gelderblom, A.J.; Guchelaar, H.J.
• Committee: Portielje, J.E.A.; Bovée, J.V.M.G.; Herpen, C.M.L. van; Hoeven, J.J.M. van der
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2019-11-05
• ISBN (print): 9789463755771
• Sponsorship: Stichting 'Een Gift voor GIST'