OBJECTIVES: The paradigm of precision medicine in cancer is to target a specific genetic aberration. Access to off label medication is limited due to uncertainty regarding effectiveness for every biomarker-tumour-drug combination. Especially for rare cancers, there is a growing need for a method to enable early access to potentially effective therapy and to obtain real world data to use for future decision making.

METHODS: In the Netherlands, a non-randomised, multi-centre basket trial, The Drug Rediscovery Protocol (DRUP) is active to specifically identify signals of clinical benefit of approved drugs used outside their label in rare, molecularly defined subsets of patients who exhausted standard of care treatment options. For each cohort, eight patients are enrolled in stage I and 16 more in stage II, if more than one response (based on RECIST 1.1) is observed in the first stage. If less than five patients show an objective tumour response or stable disease at 16 weeks, the cohort is closed. The first two stages of the DRUP trial are exploratory with free medication provided by the marketing authorisation holder (MAH). A new third stage is added.

RESULTS: The MSI cohort with off label nivolumab, which was successfully finalised, will be expanded to a third stage, This third stage with defined inclusion criteria, duration of treatment and number of patients needed, is designed to confirm the findings in the first and second stages. Medication can be partly reimbursed based on a pay for performance model. Patients start treatment with nivolumab provided by the MAH and continue on the reimbursed drug in case of adequate individual treatment response.

CONCLUSION: The pilot with a performance-based, personalised reimbursement scheme that enables access to precision medicine in rare biomarker-defined subgroups can be a step forward in delivering precision medicine in a sustainable and affordable manner.