Abstract
Background: Biomarker-guided therapy in an experimental setting has been suggested to improve patient outcomes. However, trial-specific pre-screening tests are time and tissue consuming and complicate the personalised treatment of patients eligible for early-phase clinical trials. In this study the feasibility of whole-genome sequencing (WGS) as a one-test-for-all for guided inclusion in early-phase trials was investigated. Methods: Phase I Molecular Tumor Board (MTB) at the Erasmus MC Cancer Institute reviewed patients with advanced cancer without standard-of-care treatment (SOC) options for a ‘fresh-frozen’ (FF) tumour biopsy for WGS based on clinical-pathological features. Clinical grade WGS was performed by Hartwig Medical Foundation. MTB matched the patient with a trial, if available. Results: From September 2019–March 2021, 31 patients with highly diverse tumour types underwent a tumour biopsy for WGS. The median turnaround time (TAT) was 15 days [10–42 days]. At least one actionable event was found in 84% of the patients (26/31). One-third of the patients (11/31) received matched experimental treatment. Conclusions: WGS on fresh FF biopsies is a feasible tool for the selection of personalised experimental therapy in patients with advanced cancer without SOC options. WGS is now possible in an acceptable TAT and thus could fulfil the role of a universal genomic pre-screening test.
| Original language | English |
|---|---|
| Pages (from-to) | 776-783 |
| Number of pages | 8 |
| Journal | British Journal of Cancer |
| Volume | 127 |
| Issue number | 4 |
| Early online date | 23 May 2022 |
| DOIs | |
| Publication status | Published - 1 Sept 2022 |
Bibliographical note
Funding Information:We would like to thank M. Smid, Department of Medical Oncology, Erasmus MC, Rotterdam, NL for facilitating the mutational signature analyses. We would like to thank Hartwig Medical Foundation for facilitating and supporting whole-genome sequencing data generation, data analyses and data interpretation.
Funding Information:
A-MCD reports receiving research support from AstraZeneca, Bristol-Myers Squibb and Abbvie; receiving honoraria from Amgen, Bayer, Bristol-Myers Squibb, Novartis, Roche. A-MCD reports having honoraria from Eli Lily, AstraZeneca, Jansen, Chiesi, Pfizer and Takeda; receiving grants from Amgen; having participation on a data safety monitoring board or advisory board of Boehringer Ingelheim, Amgen, Bayer, Pharmamar and Sanofi; having leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid of Roche. JHvdT reports receiving grants from Bristol-Myers Squibb and AstraZeneca; consulting fees from Bristol-Myers Squibb, Eli Lily and Roche; honoraria from Johnson & Johnson and MSD; receiving medical equipment from Roche Diagnostics. MPL reports receiving grants from Janssen Cilag B.V., Sanofi and Merck; consulting fees from Pfizer, AstraZeneca, Astellas, Merck, Novartis, Julius Clinical and Stichting Treat Meds. The remaining authors declare no competing interests.
Publisher Copyright:
© 2022, The Author(s).
