Off-label use of cancer therapies in women diagnosed with breast cancer in the United States

Abstract

PurposeTo determine the level of off-label cancer therapy use in a population of female breast cancer patients and to establish whether this use was evidence-based.MethodsA study was conducted by sampling Cerner’s data warehouse for all women diagnosed with breast cancer between January 2000 and June 2009 who received at least one cancer therapy approved by the US-FDA during the study period. Drug encounters were considered off-label if the circumstances of use did not match the age or medical diagnoses specified on the product label at the time of study. The level of evidence for the use of these drugs in a breast cancer setting was evaluated from randomized phase III trials using a tiered approach.ResultsThe study included 2,663 women with a median age of 59 years. A total of 1,636 off-label encounters were recorded, representing 13.0% of all encounters. Of the 65 cancer therapies investigated, 55.4% were prescribed off-label. The drugs with the highest off-label use were, in a descending order, vinorelbine, carboplatin, bevacizumab, leuprolide, liposomal doxorubicin and cisplatin. Most off-label encounters were evidence-based and more likely to be associated with private insurance coverage, younger age, ethnicities other than Caucasian, smaller treatment centres and drugs with limited labeled indications that have a longer market history.ConclusionsOff-label prescribing is common practice in oncology and is an integral component of breast cancer treatment strategies. While this practice tends to be associated with specific socio-demographic factors and disease characteristics, the majority of off-label encounters appear to be evidence-based.

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.…”

“…Sample size was considered suboptimal for two studies considering the study objective . Three studies also provided limited descriptions of statistical methods or how they dealt with missing data and potential source of bias . One study did not report results of multivariate analyses .…”

Off-label use of targeted therapies in oncology

“…Regarding targeted therapies, off-label use of kinase inhibitors was anecdotal (0.4% of the patients). 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] .…”

“…Off-label use concerned the timing of treatment in metastatic colorectal cancer (40%) and the use outside oncology in age-related macular degeneration (10%) [16] . More specifically, off-label use of anticancer agents has been investigated over a 10-years period (2000-2009) in a population of 2663 patients with breast cancer in the United States using an administrative data base [17] . A proportion of 13% of the patients were treated offlabel mainly with cytotoxic agents.…”