Unsupported off-label chemotherapy in metastatic colon cancer

Abstract

BackgroundNewer systemic therapies have the potential to decrease morbidity and mortality from metastatic colorectal cancer, yet such therapies are costly and have side effects. Little is known about their non-evidence-based use.MethodsWe conducted a retrospective cohort study using commercial insurance claims from UnitedHealthcare, and identified incident cases of metastatic colon cancer (mCC) from July 2007 through April 2010. We evaluated the use of three regimens with recommendations against their use in the National Comprehensive Cancer Center Network Guidelines, a commonly used standard of care: 1) bevacizumab beyond progression; 2) single agent capecitabine as a salvage therapy after failure on a fluoropyridimidine-containing regimen; 3) panitumumab or cetuximab after progression on a prior epidermal growth factor receptor antibody. We performed sensitivity analyses of key assumptions regarding cohort selection. Costs from a payer perspective were estimated using the average sales price for the entire duration and based on the number of claims.ResultsA total of 7642 patients with incident colon cancer were identified, of which 1041 (14%) had mCC. Of those, 139 (13%) potentially received at least one of the three unsupported off-label (UOL) therapies; capecitabine was administered to 121 patients and 49 (40%) likely received it outside of clinical guidelines, at an estimated cost of $718,000 for 218 claims. Thirty-eight patients received panitumumab and six patients (16%) received it after being on cetuximab at least two months, at an estimated cost of $69,500 for 19 claims. Bevacizumab was administered to 884 patients. Of those, 90 (10%) patients received it outside of clinical guidelines, at an estimated costs of $1.34 million for 636 claims.ConclusionsIn a large privately insured mCC cohort, a substantial number of patients potentially received UOL treatment. The economic costs and treatment toxicities of these therapies warrant increased efforts to stem their use in settings lacking sufficient scientific evidence.

Off-label drug use in oncology: a systematic review of literature

“…The general characteristics of various studies, such as the extent and outcomes of off‐label chemotherapies, are described in Table . There were 23 studies reporting prevalence of off‐label use . Off‐label drug use was classified as category 1 ( n = 16), category 2 ( n = 10), category 3 ( n = 12) and category 4 ( n = 11) …”

“…There was no use of formulary, guidelines, package inserts or books for defining off‐label use. Five studies gave limited or no information on baseline patient characteristics . No study provide a rationale for sample size.…”

“…For ambulatory care patients, 7%–50% of prescriptions were for off‐label use . Off‐label drug use unsupported by standard treatment guidelines, or drug compendia was in the range of 7%–31% …”

“…The most commonly administered off‐label medicines were carboplatin, doxorubicin, fluorouracil, paclitaxel, docetaxel, vinorelbine, gemcitabine and oxaliplatin . The most commonly used off‐label targeted therapies include bevacizumab, trastuzumab, cetuximab, rituximab, gefitinib and erlotinib . Bevacizumab was prescribed in an off‐label manner for the treatment of metastatic colorectal cancer in a range of 10%–62% patients .…”

Off-label use of targeted therapies in oncology

“…Off-label prescription of monoclonal antibodies was more prevalent (8% of the patients), particularly the agent anti-angiogenic bevacizumab (before the FDA cancelled the approval in breast cancer in 2011) [17] . Unsupported off-label use of the monoclonal antibodies panitumumab and bevacizumab has been retrospectively studied in a population of privatized insurance patients with metastatic colorectal cancer on progression, in the United States [18] . Between 2007 and 2010, off-label prescribing non-supported by the NCCN concerned 10% of the patients under bevacizumab and 16% of those under panitumumab.…”