Off-label use of targeted therapies in oncology

Levêque, Dominique

doi:10.5306/wjco.v7.i2.253

Cited by 28 publications

(32 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This choice is particularly relevant because further analysis of the current study was global and not just US‐centered. Third, off‐label use in oncology has extensively been studied and described, but we chose a slightly different approach, to be more aligned with routine care. Labels are stringently phrased by regulators and off‐label use then occurs as soon as a patient's condition is not strictly similar to the one depicted in the Summary of Product Characteristics.…”

Section: Discussionmentioning

confidence: 99%

Post‐marketing research and its outcome for novel anticancer agents approved by both the FDA and EMA between 2005 and 2010: A cross‐sectional study

Zeitoun

Baron

Vivot

et al. 2017

Intl Journal of Cancer

View full text Add to dashboard Cite

Post-marketing research in oncology has rarely been described. We aimed to characterize post-marketing trials for a consistent set of anticancer agents over a long period. We performed a cross-sectional analysis of post-marketing trials registered at ClinicalTrials.gov through September 2014 for novel anticancer agents approved by both the US Food and Drug Administration and the European Medicines Agency between 2005 and 2010. All relevant post-marketing trials were classified according to indication, primary outcome, starting date, sponsors, and planned enrollment. Supplemental indications were retrieved from regulatory documents and publication rate was assessed by two different methods. Ten novel anticancer agents were eligible: five were indicated for hematologic malignancies and the remaining five for solid cancers (three for kidney cancer). We identified 2,345 post-marketing trials; 1,362 (58.1%) targeted an indication other than the originally approved one. We observed extreme variations among drugs in both number of post-marketing trials (range 8-530) and overall population to be enrolled per trial (1-8,381). Post-marketing trials assessed almost all types of cancers, the three most frequently studied cancers being leukemia, kidney cancer and myeloma. In all, 6.6% of post-marketing trials had a clinical endpoint as a primary outcome, and 35.9% and 54.1% had a safety or surrogate endpoint, respectively, as a primary outcome. Nine drugs obtained approval for supplemental indications. The publication rate at 10 years was 12.3 to 26.1% depending on the analysis method. In conclusion, we found that post-marketing research in oncology is highly heterogeneous and the publication rate of launched trials is low.

show abstract

Section: Discussionmentioning

confidence: 99%

Post‐marketing research and its outcome for novel anticancer agents approved by both the FDA and EMA between 2005 and 2010: A cross‐sectional study

Zeitoun

Baron

Vivot

et al. 2017

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…but perceived efficacy, toxicity, and quality of life considerations may favor the use of an off-label medication rather than an approved treatment. 2 Off-label prescribing is common across all pediatric disciplines, though may be enriched in specific populations. 3 For example, European studies have shown that at least one-third of children in hospitals and up to 90% of neonates in a neonatal intensive care unit receive off-label therapies.…”

mentioning

confidence: 99%

Off‐label prescribing of targeted anticancer therapy at a large pediatric cancer center

et al. 2020

View full text Add to dashboard Cite

Background Off‐label drug prescribing is common in pediatric clinical medicine, though the extent and impact of this practice in pediatric oncology has not yet been characterized. Methods We completed a retrospective single‐institution cohort study evaluating prevalence, characteristics, and clinical outcomes of off‐label prescribing of 108 FDA‐approved targeted anticancer drugs in patients < 30 years old treated for cancer from 2007 to 2017. Dosing strategies were adjusted for body size and compared to FDA‐approved adult dosing regimen. A composite toxicity endpoint was defined as a patient having unplanned clinic visits, emergency department visits, or unplanned hospital admissions that were at least possibly related to the off‐label treatment. Results The overall prevalence of off‐label use of targeted therapies was 9.2% (n = 374 patients). The prevalence increased significantly over the study period (P < .0001). Patients treated off‐label were more likely to have neuro‐oncology diagnoses compared to patients not treated off‐label (46% vs 29%; P < .0001). Of the 108 potential agents, 38 (35%) were used by at least one patient. The median starting dose was below the FDA‐approved normalized dose for 44.4% of agents. Fifteen percent of patients had a complete response while receiving off‐label therapy, 38% experienced toxicity as defined, and 13% discontinued off‐label therapy due to toxicity. Conclusions In this real‐world evaluation of prescribing at a large pediatric cancer center, off‐label prescribing of FDA‐approved targeted therapies was common, increasing in prevalence, encompassed a broad sample of targeted agents, and was tolerable. Clinicians commonly start dosing below the equivalent FDA‐approved dose.

show abstract

“…Another aspect, which utilizes genome sequencing, has also been the off‐label use of targeted therapies for patients with a similar single‐ or multi‐marker mutation profile regardless of the tumor origin . This practice is very common in oncologic clinical practice and is frequently referred to as precision medicine .…”

Section: Trends In Drug Selection Strategies For Solid Tumorsmentioning

confidence: 99%

Bringing 3D tumor models to the clinic – predictive value for personalized medicine

Halfter¹,

Mayer

2017

Biotechnology Journal

View full text Add to dashboard Cite

Current decision-guiding algorithms in cancer drug treatment are based on decades of research and numerous clinical trials. For the majority of patients, this data is successfully applied for a systemic disease management. For a number of patients however, treatment stratification according to clinically based risk criteria will not be sufficient. The most effective treatment options are ideally identified prior to the start of clinical drug therapy. This review will discuss the implementation of three-dimensional (3D) cell culture models as a preclinical testing paradigm for the efficacy of clinical cancer treatment. Patient tumor-derived cells in 3D cultures duplicate the individual tumor microenvironment with a minimum of confounding factors. Clinical implementation of such personalized tumor models requires a high quality of methodological and clinical validation comparable to other biomarkers. A non-systematic literature search demonstrated the small number of prospective studies that have been conducted in this area of research. This may explain the current reluctance of many physicians and insurance providers in implementing this type of assay into the clinical diagnostic routine despite potential benefit for patients. Achieving valid and reproducible results with a high level of evidence is central in improving the acceptance of preclinical 3D tumor models.

show abstract

Off-label use of targeted therapies in oncology

Cited by 28 publications

References 30 publications

Post‐marketing research and its outcome for novel anticancer agents approved by both the FDA and EMA between 2005 and 2010: A cross‐sectional study

Post‐marketing research and its outcome for novel anticancer agents approved by both the FDA and EMA between 2005 and 2010: A cross‐sectional study

Off‐label prescribing of targeted anticancer therapy at a large pediatric cancer center

Bringing 3D tumor models to the clinic – predictive value for personalized medicine

Contact Info

Product

Resources

About