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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References

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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., … 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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