Addressing barriers to increased adoption of DPYD genotyping at a large multisite cancer center.

PURPOSE: To describe the implementation of an in-house genotyping program to detect genetic variants linked to impaired dihydropyrimidine dehydrogenase (DPD) metabolism at a large multisite cancer center, including barriers to implementation and mechanisms to overcome barriers to facilitate test adoption. SUMMARY: Fluoropyrimidines, including fluorouracil and capecitabine, are commonly used chemotherapy agents in the treatment of solid tumors, such as gastrointestinal cancers. DPD is encoded by the DPYD gene, and individuals classified as DPYD intermediate and poor metabolizers due to certain genetic variations in DPYD can experience reduced fluoropyrimidine clearance and an increased risk of fluoropyrimidine-related adverse events. Although pharmacogenomic guidelines provide evidence-based recommendations for DPYD genotype-guided dosing, testing has not been widely adopted in the United States for numerous reasons, including limited education/awareness of clinical utility, lack of testing recommendations by oncology professional organizations, testing cost, lack of accessibility to a comprehensive in-house test and service, and prolonged test turnaround time. Based on stakeholder feedback regarding barriers to testing, we developed an in-house DPYD test and workflow to facilitate testing in multiple clinic locations at Levine Cancer Institute. Across 2 gastrointestinal oncology clinics from March 2020 through June 2022, 137 patients were genotyped, and 13 (9.5%) of those patients were heterozygous for a variant and identified as DPYD intermediate metabolizers. CONCLUSION: Implementation of DPYD genotyping at a multisite cancer center was feasible due to operationalization of workflows to overcome traditional barriers to testing and engagement from all stakeholders, including physicians, pharmacists, nurses, and laboratory personnel. Future directions to scale and sustain testing in all patients receiving a fluoropyrimidine across all Levine Cancer Institute locations include electronic medical record integration (eg, interruptive alerts), establishment of a billing infrastructure, and further refinement of workflows to improve the rate of pretreatment testing.

Levine Cancer Institute Financial Toxicity Tumor Board: A Potential Solution to an Emerging Problem.

PURPOSE: Fiscal distress or "financial toxicity," in which patients experience challenges in paying for treatment, are becoming dominant problems for patients with cancer because of burgeoning health care costs and strategies implemented by health insurance payers to reduce their level of expenditure. We report the structure and function of the first Financial Toxicity Tumor Board (FTTB). Modeled on the concept of a conventional multidisciplinary tumor board, FTTB functions as a multidisciplinary conference providing broad problem-solving approaches to financial toxicity. METHODS: The FTTB, with participation from physicians, nurses, financial counselors, nurse navigators, social workers, and administrators, meets monthly and is focused on financial toxicity and financial worry experienced by patients with cancer. It is linked to a Patient Assistance Program for oncologic pharmaceutical agents as this domain constitutes a critical area of financial toxicity for many patients. RESULTS: In the first years of function, more than $55-$60 million of personal expenditure has been avoided for 1,749 and 1,819 patients, respectively, as well as more than $1.3 million copay assistance provided for financially challenged patients. Problems addressed have included payer impediments, underinsurance, complexities of certification, coding or billing issues, and inadequate internal standard operating procedures. CONCLUSION: A focus on proactive management of financial toxicity through the function of multidisciplinary FTTBs substantially ameliorates this burgeoning international problem. This concept is presented early as it may be leveraged readily in other centers.

Sunitinib in Patients with Metastatic Colorectal Cancer (mCRC) with FLT-3 Amplification: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study.

BACKGROUND: TAPUR is a pragmatic, phase II basket study evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancers harboring genomic alterations known to be drug targets. Sunitinib is an oral multikinase inhibitor of FMS-like tyrosine kinase-3 (FLT-3), among other targets. Results from a cohort of patients with metastatic colorectal cancer (mCRC) with FLT-3 amplification treated with sunitinib are reported. OBJECTIVE: This study aimed to investigate whether patients with mCRC with FLT-3 amplification would be responsive to sunitinib, an oral multikinase inhibitor. METHODS: Eligible patients received a standard sunitinib dose of 50 mg orally for 4 weeks followed by 2 weeks off. Simon's two-stage design was used with the primary study endpoint of objective response (OR) or stable disease (SD) at 16 weeks based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary endpoints were progression-free survival, overall survival, and safety. RESULTS: Ten patients were enrolled from November 2016 to April 2018. All patients had mCRC with FLT-3 amplification. No ORs were observed. Although two patients had SD at 16 weeks, one died because of disease progression shortly thereafter and the cohort was closed. A single grade 3 adverse event of diarrhea was reported as possibly related to sunitinib. CONCLUSIONS: Monotherapy with sunitinib does not have clinical activity in patients with mCRC with FLT-3 amplification and should not be prescribed for off-label use. Other treatments should be considered for these patients, including treatments offered in clinical trials. CLINICAL TRIAL REGISTRATION: NCT02693535 (26 February 2016).