Effect of a Collaboration Between a Health Plan, Oncology Practice, and Comprehensive Genomic Profiling Company from the Payer Perspective.

BACKGROUND: Comprehensive genomic profiling (CGP) is a next-generation sequencing-based methodology that detects 4 classes of genomic alterations, as well as gene signature biomarkers such as microsatellite instability and tumor mutational burden. In the context of precision oncology, CGP can help to direct treatment to genomically matched therapies. OBJECTIVE: To describe the results of a 3-year observational analysis of patients undergoing testing with CGP assays (either FoundationOne or FoundationOne Heme) at a community oncology practice after a regional health plan implemented a medical policy that enabled coverage of CGP. METHODS: A retrospective analysis of medical records was completed at the oncology practice from November 2013 to January 2017; this date range was chosen to coincide with the regional health plan's medical policy implementation of CGP. The medical policy provided coverage of CGP for patients with advanced solid and hematologic cancers. A medical record review assessed all previous and current molecular test results, matched therapy or clinical trial enrollment, and clinical outcomes (clinical benefit or disease progression). The potential cost diversion, from payer to study sponsor, for patients who enrolled in clinical trials was explored. RESULTS: There were 96 patients in the community oncology practice who received CGP over the 3-year period, 86 of whom had clinically relevant genomic alterations. Of the 86, 15 patients were treated with genomically matched therapy, and 6 patients enrolled in clinical trials based on CGP results. In a subset of 32 patients who previously underwent conventional testing, most (84%) had clinically relevant genomic alterations detected by CGP that conventional testing did not identify, and a portion of these patients subsequently received treatment based on the CGP results. In the separate cost diversion analysis of 20 patients who enrolled in phase 1 clinical trials, an estimated $25,000 per-patient cost-benefit may have been accrued to the payer. CONCLUSIONS: This observational analysis characterized the use of CGP in a large community oncology practice among a group of patients insured by a regional health plan. Clinical trial enrollment was facilitated by CGP use in the community setting and may have contributed to cost diversion from the payer to study sponsors. DISCLOSURES: No separate study-related funding was provided by or to Priority Health, Foundation Medicine, and Cancer and Hematology Centers of West Michigan. Data analysis by Reitsma was conducted as part of an internship funded by Priority Health. Reitsma and Fox are employed by Priority Health. Anhorn, Vanden Borre, Cavanaugh, Chudnovsky, and Erlich are employed by Foundation Medicine.

Genetic Analysis of 779 Advanced Differentiated and Anaplastic Thyroid Cancers.

Purpose: To define the genetic landscape of advanced differentiated and anaplastic thyroid cancer (ATC) and identify genetic alterations of potential diagnostic, prognostic, and therapeutic significance.Experimental Design: The genetic profiles of 583 advanced differentiated and 196 ATCs generated with targeted next-generation sequencing cancer-associated gene panels MSK-IMPACT and FoundationOne were analyzed.Results: ATC had more genetic alterations per tumor, and pediatric papillary thyroid cancer had fewer genetic alterations per tumor when compared with other thyroid cancer types. DNA mismatch repair deficit and activity of APOBEC cytidine deaminases were identified as mechanisms associated with high mutational burden in a subset of differentiated thyroid cancers and ATCs. Copy number losses and mutations of CDKN2A and CDKN2B, amplification of CCNE1, amplification of receptor tyrosine kinase genes KDR, KIT, and PDGFRA, amplification of immune evasion genes CD274, PDCD1LG2, and JAK2, and activating point mutations in small GTPase RAC1 were associated with ATC. An association of KDR, KIT, and PDGFRA amplification with the sensitivity of thyroid cancer cells to lenvatinib was shown in vitro Three genetically distinct types of ATCs are proposed.Conclusions: This large-scale analysis describes genetic alterations in a cohort of thyroid cancers enriched in advanced cases. Many novel genetic events previously not seen in thyroid cancer were found. Genetic alterations associated with anaplastic transformation were identified. An updated schematic of thyroid cancer genetic evolution is proposed. Clin Cancer Res; 24(13); 3059-68. ©2018 AACR.