Abstract Anticancer drugs are frequently used off-label for tumours that are genetically similar to the approved indication. However, outcomes are rarely captured systematically, limiting evidence-based decision-making and risking repeated futile treatment. The Drug Rediscovery Protocol (DRUP; ClinicalTrials.gov ID: NCT02925234 ) prospectively evaluates such off-label use in patients in the Netherlands with advanced solid tumours who lack standard treatment options and harbour actionable genomic alterations 1 . Here we present results of 1,610 patients who began treatment with 37 different off-label drugs between July 2016 and May 2024 in the DRUP trial. Of these patients, 1,363 were response-evaluable, including 533 (39.1%) with rare cancers. The clinical benefit rate (confirmed response or stable disease for at least 16 weeks) was 34.9% (95% confidence interval, 32.2–37.6) and the objective response rate was 15.7% (95% confidence interval, 13.7–17.9).…