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Proffered Paper session: Genomic characterization of cancer cells to guide precision medicine: Next steps

7182 - Drug Rediscovery Protocol: Expanded use of existing anticancer drugs

Date

29 Sep 2019

Session

Proffered Paper session: Genomic characterization of cancer cells to guide precision medicine: Next steps

Topics

Cytotoxic Therapy;  Targeted Therapy;  Immunotherapy;  Translational Research;  Rare Cancers

Tumour Site

Oesophageal Cancer;  Colon and Rectal Cancer

Presenters

Emile Voest

Citation

Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093/annonc/mdz394

Authors

E.E. Voest1, D.L. van der Velden2, L. Hoes2, H. Van Der Wijngaart3, M. Van Berge Henegouwen4, E. Van Werkhoven5, P. Roepman6, A.D.R. Huitema7, C. van Herpen8, D.J. de Groot9, L. Devriese10, M.J.A. de Jonge11, M. Chalabi12, E.F. Smit13, N. Mehra8, M. Labots14, S. Sleijfer11, E. Cuppen15, H.M.W. Verheul16, H. Gelderblom17

Author affiliations

  • 1 Department Of Medical Oncology, Netherlands Cancer Institute/Antoni van Leeuwenhoek hospital (NKI-AVL), 1066 CX - Amsterdam/NL
  • 2 Molecular Oncology, Netherlands Cancer Institute/Antoni van Leeuwenhoek hospital (NKI-AVL), 1066 CX - Amsterdam/NL
  • 3 Medical Oncology, VU University Medical Centre, 1007 MB - Amsterdam/NL
  • 4 Medical Oncology, Netherlands Cancer Institute, NKI AVL, 1066 CX - Amsterdam/NL
  • 5 Department Of Biometrics, The Netherlands Cancer Institute, 1066CX - Amsterdam/NL
  • 6 Oncology, Hartwig Medical Foundation, 1098XH - Amsterdam/NL
  • 7 Pharmacy & Pharmacology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 8 Medical Oncology, Radboud University Medical Center, 6525 GA - Nijmegen/NL
  • 9 Medical Oncology Dept, University Hospital Groningen (UMCG), 9700 RB - Groningen/NL
  • 10 Huispostnummer Q05.4.300 - Cancer Center Medische Oncologie, UMC-University Medical Center Utrecht, 3584 CX - Utrecht/NL
  • 11 Medical Oncology, Erasmus MC Daniel den Hoed Cancer Center, 3075EA - Rotterdam/NL
  • 12 Medical Oncology, Netherlands Cancer Institute NKI AVL, 1066 CX - AMSTERDAM/NL
  • 13 Pulmonary Diseases Dept, Netherlands Cancer Institute/Antoni van Leeuwenhoek hospital (NKI-AVL), 1066 CX - Amsterdam/NL
  • 14 Medical Oncology, Amsterdam University Medical Centers, 1105AZ - Amsterdam/NL
  • 15 Molecular Diagnostics, Hartwig Medical Foundation, 1098XH - Amsterdam/NL
  • 16 Medical Oncology, Radboud UMC, 6525 GA - Nijmegen/NL
  • 17 Medical Oncology Dept, Leids Universitair Medisch Centrum (LUMC), 2333 ZA - Leiden/NL

Resources

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Abstract 7182

Background

Large-scale genetic tumor profiling can identify increasing numbers of potentially actionable molecular variants for which approved anti-cancer drugs are available. In daily practice, however, when patients with such variants are treated with drugs outside of their approved label, successes and failures are not systematically collected or shared.

Methods

We initiated the Drug Rediscovery Protocol (DRUP), an innovative and adaptive precision oncology trial aimed at identifying signals of activity in cohorts of patients with defined tumor types and molecular variants, treated with anti-cancer drugs outside their approved label. Eligible patients have exhausted (or declined) standard therapies and have malignancies with potentially actionable variants for which no approved anti-cancer drugs are available.

Results

Here, we show an overall clinical benefit rate (defined as complete or partial response, or stable disease ≥16 weeks) of 34% in the first 215 treated patients. This comprised 136 patients who received targeted therapies, and 79 patients who received immunotherapy. Overall median clinical benefit duration was nine months (95% CI 8 – 11 months), including 26 patients with ongoing clinical benefit at data cutoff. The potential of DRUP was illustrated by the identification of a successful cohort of patients with microsatellite instable tumors receiving nivolumab, and a cohort of colorectal cancer patients with relatively low mutational load with limited clinical benefit from immunotherapy.

Conclusions

The DRUP hereby facilitates defined use of approved drugs beyond their label in (rare) cancer subgroups, identifies early signals of activity in these subgroups, accelerates clinical translation of new insights, and creates a publicly available knowledge-base for future decision making.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Netherlands Cancer Institute.

Funding

Hartwig Medical Foundation, Dutch Cancer Society, Barcode for Life, Roche, Novartis, MSD, GSK, Pfizer, AstraZeneca, BMS.

Disclosure

E.E. Voest: Research grant / Funding (self), Legally responsible for all contracts: All pharma. C. van Herpen: Advisory / Consultancy: Bayer; Advisory / Consultancy, Research grant / Funding (self): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (self): Ipsen; Advisory / Consultancy, Research grant / Funding (self): MSD; Advisory / Consultancy: Regeneron; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Merck; Research grant / Funding (self): Novartis; Research grant / Funding (self): Sanofi. M. Chalabi: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Netherlands Cancer Institute. E.F. Smit: Honoraria (institution), Research grant / Funding (institution): AstraZeneca; Honoraria (institution), Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (institution): Bayer; Honoraria (institution), Advisory / Consultancy: Eli Lilly; Honoraria (institution), Research grant / Funding (institution): MSD; Honoraria (institution), Research grant / Funding (institution): Merck; Honoraria (institution): Novartis ; Honoraria (institution): Pfizer; Honoraria (institution): Takeda; Honoraria (institution): Regeneron; Honoraria (institution), Research grant / Funding (institution): Roche Genentech; Honoraria (institution): Seattle Genetics. N. Mehra: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Bayer; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Research grant / Funding (institution): Janssen-Cilag; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Astellas; Advisory / Consultancy, Research grant / Funding (institution): Sanofi. E. Cuppen: Honoraria (institution), Advisory / Consultancy: Illumina; Honoraria (self), Advisory / Consultancy: InteRNA Technologies; Full / Part-time employment, Officer / Board of Directors: Hartwig Medical Foundation. H.M.W. Verheul: Honoraria (institution), Advisory / Consultancy: Glycostem; Honoraria (institution), Advisory / Consultancy: Lava Therapeutics. H. Gelderblom: Research grant / Funding (institution): Five Prime; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Debio; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Teva. All other authors have declared no conflicts of interest.

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