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.

Alveolar Rhabdomyosarcoma in a 69-Year-Old Woman Receiving Glucagon-Like Peptide-2 Therapy.

A 69-year-old woman was diagnosed with alveolar rhabdomyosarcoma (ARMS) of the nasopharynx. She has a history of catastrophic thromboembolic event in the abdomen that caused short-gut syndrome and dependence on total parenteral nutrition (TPN) twelve hours per day. She was treated for short-gut syndrome with teduglutide, a glucagon-like peptide-2 (GLP-2) analog, which led to reduction of TPN requirements. However, a few months later, she developed metastatic alveolar rhabdomyosarcoma. Though a causative relationship is unlikely between the peptide and ARMS due to the brief time course between teduglutide therapy and sarcoma diagnosis, neoplastic growth may have been accelerated by the GLP-2 analog, causing release of IGF-1. The transmembrane receptor for IGF-1 is frequently overexpressed in ARMS and is implicated in cell proliferation and metastatic behavior. This case describes a rare incidence of metastatic alveolar rhabdomyosarcoma in a sexagenarian and possibly the first case reported associated with the use of teduglutide. Teduglutide was discontinued due to a potential theoretical risk of acceleration of sarcoma growth, and the patient's rhabdomyosarcoma is in remission following sarcoma chemotherapy.

(90)Y-clivatuzumab tetraxetan with or without low-dose gemcitabine: A phase Ib study in patients with metastatic pancreatic cancer after two or more prior therapies.

BACKGROUND: For patients with metastatic pancreatic adenocarcinoma, there are no approved or established treatments beyond the 2nd line. A Phase Ib study of fractionated radioimmunotherapy was undertaken in this setting, administering (90)Y-clivatuzumab tetraxetan (yttrium-90-radiolabelled humanised antibody targeting pancreatic adenocarcinoma mucin) with or without low radiosensitising doses of gemcitabine. METHODS: Fifty-eight patients with three (2-7) median prior treatments were treated on Arm A (N=29, (90)Y-clivatuzumab tetraxetan, weekly 6.5 mCi/m(2)doses×3, plus gemcitabine, weekly 200 mg/m(2) doses×4 starting 1 week earlier) or Arm B (N=29, (90)Y-clivatuzumab tetraxetan alone, weekly 6.5 mCi/m(2)doses×3), repeating cycles after 4-week delays. Safety was the primary endpoint; efficacy was also evaluated. RESULTS: Cytopaenias (predominantly transient thrombocytopenia) were the only significant toxicities. Fifty-three patients (27 Arm A, 26 Arm B, 91% overall) completed ⩾1 full treatment cycles, with 23 (12 Arm A, 11 Arm B; 40%) receiving multiple cycles, including seven (6 Arm A, 1 Arm B; 12%) given 3-9 cycles. Two patients in Arm A had partial responses by RECIST criteria. Kaplan-Meier overall survival (OS) appeared improved in Arm A versus B (hazard ratio [HR] 0.55, 95% CI: 0.29-0.86; P=0.017, log-rank) and the median OS for Arm A versus Arm B increased to 7.9 versus 3.4 months with multiple cycles (HR 0.32, P=0.004), including three patients in Arm A surviving >1 year. CONCLUSIONS: Clinical studies of (90)Y-clivatuzumab tetraxetan combined with low-dose gemcitabine appear feasible in metastatic pancreatic cancer patients beyond 2nd line and a Phase III trial of this combination is now underway in this setting.

Early-phase clinical trials in the community: results from the national cancer institute community cancer centers program early-phase working group baseline assessment.

PURPOSE: The National Cancer Institute (NCI) Community Cancer Centers Program (NCCCP) formed an Early-Phase Working Group to facilitate site participation in early-phase (EP) trials. The Working Group conducted a baseline assessment (BA) to describe the sites' EP trial infrastructure and its association with accrual. METHODS: EP accrual and infrastructure data for the sites were obtained for July 2010-June 2011 and 2010, respectively. Sites with EP accrual rates at or above the median were considered high-accruing sites. Analyses were performed to identify site characteristics associated with higher accrual onto EP trials. RESULTS: Twenty-seven of the 30 NCCCP sites participated. The median number of EP trials open per site over the course of July 2010-June 2011 was 19. Median EP accrual per site was 14 patients in 1 year. Approximately half of the EP trials were Cooperative Group; most were phase II. Except for having a higher number of EP trials open (P = .04), high-accruing sites (n = 14) did not differ significantly from low-accruing sites (n = 13) in terms of any single site characteristic. High-accruing sites did have shorter institutional review board (IRB) turnaround time by 20 days, and were almost three times as likely to be a lead Community Clinical Oncology Program site (small sample size may have prevented statistical significance). Most sites had at least basic EP trial infrastructure. CONCLUSION: Community cancer centers are capable of conducting EP trials. Infrastructure and collaborations are critical components of success. This assessment provides useful information for implementing EP trials in the community.

A CD20 tandem-epitope immunogen elicits antibody in mice that binds murine cell surface CD20 and depletes splenic B cells in vivo.

CD20 is an important target for monoclonal antibody therapy of B-cell malignancies and for some autoimmune disorders. Though there is interest in evaluating the induction of active immunity to CD20 in the mouse model, the CD20 extracellular domain (ECD) has significant secondary and tertiary structure which make it difficult to target using peptide immunogens. We constructed, expressed, and purified a recombinant immunogen, CD20ECD-6, which displays six tandemly repeated copies of the C-terminus of the murine CD20 ECD covalently linked to maltose-binding protein. Analysis of the purified protein suggested a complex conformation as the protein migrated in significantly retarded fashion by SDS-PAGE analysis. Immunization of mice and rabbits with the CD20ECD-6 led to the induction of antibodies reactive with the C-terminal ECD peptide sequence by ELISA and more importantly, with native cell surface CD20 on the murine B-cell lymphomas, 38C13 and A20. Immunoprecipitation using the rabbit antisera and non-denaturing detergent confirmed the identity of the bound cell surface protein as murine CD20 and suggested that the cell-binding antibodies were specific for the native, folded conformation. Finally, immunization of mice with the CD20ECD-6 using Freund's or QS-21 adjuvants was shown to exert significant biological effects in vivo with the pronounced depletion of splenic B cells. The tandem-epitope immunogen represents a promising tool for eliciting and studying active autoimmunity to CD20, as a basis for potential development of new immunotherapeutics for cancer and autoimmune diseases.