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
3611 - Phase II trial of SM 88 in Non-Metastatic Biochemical Recurrent Prostate Cancer.
Presenter: Benjamin Gartrell
Session: Poster Display session 3
Resources:
Abstract
2492 - A phase 1 study of Ad5 PSA/MUC-1/Brachyury Vaccine in Patients with Metastatic Castration Resistant Prostate Cancer (mCRPC)
Presenter: Marijo Bilusic
Session: Poster Display session 3
Resources:
Abstract
3142 - Multicenter Phase I Trial of a DNA Vaccine Encoding the Androgen Receptor Ligand Binding Domain (pTVG-AR, MVI-118) in Patients with Metastatic Prostate Cancer
Presenter: Douglas McNeel
Session: Poster Display session 3
Resources:
Abstract
4327 - Impact of germline mutations in Homologous Recombination (HR) genes on the response to Radium-223 for metastatic castration resistant prostate cancer (mCRPC)
Presenter: Elena Castro
Session: Poster Display session 3
Resources:
Abstract
3600 - Serum biomarkers of bone metabolism in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) treated with Radium-223 (Ra223): Results from a prospective multicentre study
Presenter: Nuria Romero Laorden
Session: Poster Display session 3
Resources:
Abstract
3742 - Prognostic value of tumor suppression genes (TP53, PTEN, Rb) in metastatic hormone sensitive prostate cancer
Presenter: Miguel Gonzalez Velez
Session: Poster Display session 3
Resources:
Abstract
2643 - Germline sequencing of advanced prostate cancer patients in the BARCODE2 trial
Presenter: Sarah Benafif
Session: Poster Display session 3
Resources:
Abstract
4349 - Impact of treatment sequence in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): data from the prospective PROREPAIR-B study.
Presenter: Carlo Cattrini
Session: Poster Display session 3
Resources:
Abstract
3301 - Implications of Single Nucleotide Polymorphisms (SNPs) in Androgen Related-Genes in Outcome of metastatic castration-resistant prostate cancer (mCRPC) patients treated with Abiraterone (Abi) and Enzalutamide (Enza)
Presenter: Isabel Aragon
Session: Poster Display session 3
Resources:
Abstract
2275 - Activating mutations in AKT1/PIK3CA are associated with poor clinical outcomes in metastatic prostate cancer (mPC)
Presenter: Simon Fu
Session: Poster Display session 3
Resources:
Abstract