Many molecular tumor agnostic targets for therapy and consequent molecular targeted treatments have been discovered in the last decade. However, identifying patients with actionable mutations is impeded by the lack of routinely performed comprehensive molecular testing. This strongly limits the opportunity for a patient to receive personalized treatment with a targeting compound in a clinical trial. In this study, we investigate feasibility of the most comprehensive DNA sequencing platform: Whole Genome Sequencing (WGS) as a tool to select individualized experimental treatment for patients.
The Phase I Molecular Tumor Board, Erasmus MC Cancer Institute discussed if a patient with advanced cancer without standard-of-care treatment options should undergo a tumor biopsy (fresh frozen) for WGS based on clinical-pathological features. Clinical grade WGS was performed by Hartwig Medical Foundation. Actionability was reported using the ESCAT scale. Based on the results, a matched trial was offered to the patient if available.
From Sept 2019 to March 2021, 31 patients, all with a different tumor type, underwent a WGS biopsy. Median age was 59 years (32-79), median ECOG score was 1 (0-1) and median Royal Marsden Hospital prognostic score was 1 (0-2). Median turnaround time (TAT) between the biopsy and WGS reporting was 15 calendar days. 2 samples were not evaluable due to low tumor purity. Most of the tumors (25/29) harbored an actionable event of ≥ ESCAT level 4. 11 patients received a matched experimental treatment. The reasons for not receiving matched treatment were the absence of a matching trial (n=8), rapid clinical deterioration (n=4) or other (n=2).
We conclude that in this patient population WGS is a feasible tool for personalized experimental treatment selection with a clinically relevant TAT. WGS revealed at least one actionable target in the majority of the tested tumors and almost 40% of the patients received a matched treatment in a clinical trial based on the WGS outcome. For many potential targets no trial was available at our and adjacent institutes. The current clinical trial designs need to evolve to accommodate a more personalized experimental treatment selection for patients.
Clinical trial identification
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Has not received any funding.
All authors have declared no conflicts of interest.