Abstract 3282
Background
Advances in DNA sequencing technology have strongly reduced costs of Whole Genome Sequencing (WGS) and have made it possible to perform WGS on tumor biopsies within 2 to 3 weeks. Despite its great potential, the value of WGS has so far only been addressed in retrospective or small prospective studies. We have retrospectively shown in > 2,400 metastatic cancer patients that in 31% an approved biomarker for a targeted treatment could be identified. Of these biomarkers, 58% were not targets for standard-of-care (SoC) treatment but suggested off-label use or clinical study eligibility. The potential of WGS in a routine diagnostic setting is explored in the WIDE study and will address feasibility, clinical validity and added value of WGS.
Methods
WGS will be performed on a prospective cohort of 1200 patients with (suspicion of) stage IV metastatic cancer including all solid tumor types. WGS is conducted at the Hartwig Medical Foundation independently of, and in parallel with, SoC diagnostics at the Netherland Cancer Institute. Results are discussed in a tumor board to assess the value of WGS findings for treatment decision and clinical study eligibility. In addition, cost-effectiveness will be evaluated and all participating treating physicians will be asked to what extent WGS has aided their decisions making.
Results
With an accrual rate of 50-75 patients/month starting end of Q2 2019, results of the first 200 patients will be presented. Data from 25 retrospective cases (all with WGS, and 13 with parallel SoC MDx) indicated targets for standard targeted treatment in 5 patients (EGFR, ERBB2 and ROS1 inhibitors) and were identified both WGS and SoC MDx. In 19 patients, WGS found potential clinical study eligibility targets (including PI3K/mTOR, CDK4/6, MEK, FGFR1, MDM2, PARP and checkpoint inhibitors), whereas SoC MDx identified only 6 of these patients as potentially eligible. No relevant DNA aberration was identified for 5 patients.
Conclusions
The WIDE study will provide quantifiable data regarding the feasibility, clinical validity and added value of WGS analysis for patients with metastatic cancer in a routine clinical diagnostic setting.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Netherlands Cancer Institute.
Funding
Illumina.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
1908 - Androgen Receptor (AR) Aberrations in Patients (Pts) With Metastatic Castration-Sensitive Prostate Cancer (mCSPC) Treated With Apalutamide (APA) Plus Androgen Deprivation Therapy (ADT) in TITAN
Presenter: Kim Chi
Session: Poster Display session 3
Resources:
Abstract
4058 - 68Ga-PSMA guided bone biopsies for molecular diagnostics in metastatic castration resistant prostate cancer patients
Presenter: Anouk de Jong
Session: Poster Display session 3
Resources:
Abstract
2226 - Spatial-Temporal Change in Quantitative Total Bone Imaging (QTBI) and Circulating Tumor Cells (CTCs) in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated With Enzalutamide (ENZA)
Presenter: Glenn Liu
Session: Poster Display session 3
Resources:
Abstract
5795 - Efficacy of Enzalutamide in Hormone-sensitive Metastatic Prostate Cancer: Clinical Utility of 18F-Choline PET and Whole Body MRI.
Presenter: Susanne Osanto
Session: Poster Display session 3
Resources:
Abstract
899 - Urine extracellular vesicle GATA2 mRNA alone and in a multigene test predicts initial prostate biopsy result
Presenter: Jungreem Woo
Session: Poster Display session 3
Resources:
Abstract
3094 - Circulating tumor cell (CTC) genomic landscape in neuroendocrine prostate cancer (NEPC) by single cell copy number analysis
Presenter: Vincenza Conteduca
Session: Poster Display session 3
Resources:
Abstract
2527 - Circulating Tumor Cells (CTC) count and Prostate-Specific Antigen (PSA) response measures in metastatic Castration-Resistant Prostate Cancer (mCRPC) patients (pts) treated with Docetaxel (Doc)
Presenter: Rebeca Lozano Mejorada
Session: Poster Display session 3
Resources:
Abstract
6106 - Assessing the clinical relevance of drug–drug interactions (DDI) with darolutamide (DARO)
Presenter: Christian Zurth
Session: Poster Display session 3
Resources:
Abstract
2237 - KEYNOTE-921: phase 3 study of pembrolizumab (pembro) plus docetaxel and prednisone for enzalutamide (enza)- or abiraterone (abi)-pretreated patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).
Presenter: Daniel Petrylak
Session: Poster Display session 3
Resources:
Abstract
2241 - KEYNOTE-641: Phase 3 Study of Pembrolizumab (pembro) Plus Enzalutamide for Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Presenter: Julie Graff
Session: Poster Display session 3
Resources:
Abstract