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

Authors

  • Soemeya F. Haj Mohammad Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands; Department of Molecular Oncology & Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands https://orcid.org/0000-0002-7339-1714
  • Hans J.L. Timmer Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands; Department of Molecular Oncology & Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands https://orcid.org/0009-0002-3822-7326
  • Laurien J. Zeverijn Department of Molecular Oncology & Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands
  • Birgit S. Geurts Department of Molecular Oncology & Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands
  • Ilse A.C. Spiekman Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands https://orcid.org/0009-0008-9827-1138
  • Karlijn Verkerk Department of Molecular Oncology & Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands https://orcid.org/0000-0002-5882-4980
  • Florentine A.J. Verbeek Department of Molecular Oncology & Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands https://orcid.org/0009-0002-7406-8748
  • Henk M.W. Verheul Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands https://orcid.org/0000-0001-5981-922X
  • Emile E. Voest Department of Molecular Oncology & Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands https://orcid.org/0000-0001-8249-9586
  • Hans Gelderblom Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands https://orcid.org/0000-0001-9270-8636

DOI:

https://doi.org/10.2340/1651-226X.2024.34885

Keywords:

targeted therapy, immunotherapy, whole genome sequencing, precision medicine

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.

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Published

2024-05-23

How to Cite

Haj Mohammad, S. F., Timmer, H. J. ., Zeverijn, L. J., Geurts, B. S., Spiekman, I. A., Verkerk, K., Verbeek, F. A., Verheul, H. M., Voest, E. E., & Gelderblom, H. (2024). The evolution of precision oncology: The ongoing impact of the Drug Rediscovery Protocol (DRUP). Acta Oncologica, 63(1), 368–372. https://doi.org/10.2340/1651-226X.2024.34885

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