Mapping off-label use and reimbursement pathways for oncology drugs in The Netherlands: a cross-sectional observational study.

BACKGROUND: Off-label use of anticancer medicines is common. Investigator-initiated trials evaluating off-label indications often do not result in label expansion. Additionally, off-label use is often considered when approved treatments are lacking or exhausted. Such use may lead to uncertain efficacy and safety and poses reimbursement challenges. This study examines the Dutch framework to evaluate off-label indications for population-level reimbursement. We quantify national off-label oncology drug use and analyse its supporting evidence to identify clinical needs and support policy development. MATERIALS AND METHODS: We identified reimbursable oncology indication-drug pairs (IDPs) using the World Health Organization Anatomical Therapeutic Chemical classification. Approved and off-label indications were mapped using European Medicines Agency marketing authorisations, European Society for Medical Oncology guidelines, medical literature, and the national medicines database. National 2023 health care registry data were analysed to quantify off-label prescribing and expenditure for high-cost oncology drugs. Evidence supporting selected off-label treatments was evaluated using public assessment reports and clinical guidelines. RESULTS: As of January 2025, 331 of 930 (35.6%) reimbursable oncology IDPs were off-label, mainly involving high-cost drugs (n = 299 of 331, 90.3%). Off-label treatments frequently involved chemotherapy, accounting for 67.1% (n = 163 of 331) of off-label IDPs. Targeted therapies comprised 32.9% (n = 109 of 331). For high-cost drugs, 24.4% (n = 41 238 of 169 043) of prescriptions were off-label in 2023, representing only 2.3% (€30.3 million of €1.3 billion) of total expenditure on these drugs. Targeted therapies posed the largest financial impact, representing 67.7% (€20.5 of €30.3 million) of off-label expenditure. The Dutch framework reimbursed off-label treatments meeting thresholds for clinical benefit. Frequently used off-label treatments were supported by strong evidence. Evidence levels varied for rarer indications. CONCLUSIONS: The high prevalence of off-label oncology treatments in The Netherlands underscores the importance of a framework to evaluate off-label indications for reimbursement, ensuring access to effective and financially sustainable treatments. It also highlights the need for policy reform to encourage regulatory approval.