1408PWGS implementation in standard cancer diagnostics for every cancer patient (WIDE)

Abstract 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. Legal entity responsible for the study Netherlands Cancer Institute. Funding Illumina. Disclosure All authors have declared no conflicts of interest.