The evolution of precision oncology: The ongoing impact of the Drug Rediscovery Protocol (DRUP)

Abstract

Background and purpose: The Drug Rediscovery Protocol (DRUP) is a Dutch, pan-cancer, nonrandomized clinical trial that aims to investigate the efficacy and safety of targeted and immunotherapies outside their registered indication in patients with advanced or metastatic cancer. Patients: Patients with advanced or metastatic cancer are eligible when there are no standard of care treatment options left and the tumor possesses a molecular genomic variant for which commercially available anticancer treatment is accessible off-label in DRUP. Clinical benefit is the study’s primary endpoint, characterized by a confirmed objective response or stable disease after at least 16 weeks of treatment. Results: More than 2,500 patients have undergone evaluation, of which over 1,500 have started treatment in DRUP. The overall clinical benefit rate (CBR) remains 33%. The nivolumab cohort for patients with microsatellite instable metastatic tumors proved highly successful with a CBR of 63%, while palbociclib or ribociclib in patients with tumors harboring CDK4/6 pathway alterations showed limited efficacy, with a CBR of 15%. The formation of two European initiatives (PCM4EU and PRIME-ROSE) strives to accelerate implementation and enhance data collection to broaden equitable access to anticancer treatments and gather more evidence. Conclusion: DRUP persists in improving patients access to off-label targeted or immunotherapy in the Netherlands and beyond. The expansion of DRUP-like clinical trials across Europe provides countless opportunities for broadening the horizon of precision oncology.

Acta Oncologica Nordic Precision Cancer Medicine Symposium 2023 – merging clinical research and standard healthcare

“…The trial opened in 2016 and key elements to the DRUP success include MTBs, good research infrastructures, and involvement of payers and pharmaceutical companies. The latest update from the DRUP trial is presented by Mohammad et al in this special edition [8]. Moreover, Gelderblom described how the first stage three expansion cohort using nivolumab for treatment of dMMR/MSI solid tumours met evaluation criteria, resulting in reimbursement of this treatment since July 2022 in the Netherlands.…”