Abstract LB-230: A prospective clinical trial to evaluate DNA sequencing as a diagnostic tool to guide cancer therapy: results from the initial 50 patients

Abstract Background:We are conducting a multicenter clinical trial to evaluate the feasibility of including next-generation sequencing in routine clinical care. Study goals are to determine patient acceptance of research biopsies for genomic sequencing, optimal methods and procedures for sample collection, DNA extraction for successful analysis, review and reporting of mutations back to clinicians and patients with three weeks. Methods: Patients (pts) with metastatic cancer potentially eligible for clinical trials are recruited from 4 cancer centers. A tumor biopsy, blood sample and archived tumor specimens are collected from consenting patients. DNA from samples are analyzed using Pacific Biosciences RS targeted gene sequencing and Sequenom Oncocarta™ V1.0 genotyping. Detected mutations are validated in a CAP/CLIA certified laboratory. An expert panel of clinicians and scientists review results to determine whether results are actionable and reportable to clinicians. Results: As of 01/2012, 50 pts have been recruited. Pt demographics include median age = 57; primary tumor colorectal 9 pts (18%), breast 8 (16%), ovary 8 (16%), lung 5 (10%), others 20 (40%); median number prior treatments = 3; median time with metastatic disease = 17 months. Over 90% of approached pts consented to the study. Molecular profiling by Pacific Biosciences RS and Sequenom was successful in 43 pts (86%) with 100% concordance between genomic platforms. Somatic mutations were identified in over 30% of pts; 75% of these (including mutations in KRAS, PIK3CA, EGFR, RET, KIT) were deemed actionable. Seven pts (14%) had treatment impacted by matching a targeted therapy to the genetic profile; 4 patients had benefit (1 PR in ovarian cancer, 1 SD in breast cancer, 2 clinical benefits in thyroid and unknown primary squamous cell cancers). Four pts had novel mutations in AKT1, PDGFRA, EGFR and KRAS not present on the Oncocarta panel demonstrating the added benefit of sequencing the entire exon. Genomic results from of archived tumor specimens and fresh tumor biopsies matched in 26 of 30 patients (90%) with paired samples. 62% of pts had delivery of a clinical report within