Increased long QT and torsade de pointes reporting on tamoxifen compared with aromatase inhibitors

Grouthier, Virginie; Lebrun‐Vignes, Bénédicte; Glazer, Andrew M.; Touraine, Philippe; Funck‐Brentano, Christian; Pariente, Alexandre; Courtillot, Carine; Bachelot, Anne; Roden, Dan M.; Moslehi, Javid; Salem, Joe‐Elie

doi:10.1136/heartjnl-2017-312934

Cited by 43 publications

(36 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…36 Although the prescribing information for tamoxifen, 37 capecitabine, 38 and fluorouracil 39 do not include a specific warning about QTc prolongation, previous studies have reported an increased risk of QTc prolongation associated with these medications in patients with cancer. 40,41 The present analysis has several limitations. First, molecular profiling data were not available in the databases, and identification of patients with HR+/ HER2-mBC was therefore based on targeted treatment history only.…”

Section: Risk Factormentioning

confidence: 88%

Risk Factors of QTc Prolongation in Women With Hormone Receptor‒positive/Human Epidermal Growth Factor Receptor 2‒negative Metastatic Breast Cancer: A Retrospective Analysis of Health Care Claims Data

Ward

Harnett

Bell

et al. 2019

Clinical Therapeutics

View full text Add to dashboard Cite

Purpose: In addition to biomarker status, treatment selection for metastatic breast cancer (mBC) includes individual patient and clinical characteristics such as tumor burden, timing of disease recurrence, and comorbidities. Women with mBC may take medications that can increase the risk of drug-induced toxicities, including prolongation of cardiac repolarization (prolongation of QT interval). Corrected QT (QTc) prolongation, a toxicity associated with many cancer treatments, can lead to potentially life-threatening ventricular arrhythmias. As such, it is important to identify patients at risk for QTc prolongation due to comorbid conditions, concomitant medications, or electrolyte abnormalities. This real-world study estimated the proportion of women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) mBC who may be at risk of developing QTc prolongation. Results in the elderly are also included. Methods: This retrospective, cross-sectional cohort study used the Truven Health MarketScan and Optum Clinformatics administrative claims databases. Patients' medical and pharmacy data were evaluated to assess the risk of QTc prolongation. Prescription and medication administration claims were evaluated during the 7-day period before the index date (ie, first secondary neoplasm diagnosis). In addition, International Classification of Diseases, Ninth/Tenth Revision, Clinical Modification, codes were evaluated 12 months before the index date to describe congenital long QT syndrome, cardiac disease, and electrolyte abnormalities. Findings: A cohort of 24,340 women with HR+/ HER2-mBC were identified, including 5059 women aged 65e74 years and 4851 aged 75 years. Based on an overall analysis of risk factors (congenital long QT syndrome, cardiovascular disease, electrolyte abnormalities, or concomitant medications), 29.5% of all patients, 33.2% of patients aged 65e74 years, and 40.5% of patients aged 75 years had risk factors for QTc prolongation. Implications: This analysis of real-world data indicates that almost 1 in 3 women with HR+/HER2-mBC had congenital long QT syndrome, cardiovascular disease, and/or electrolyte abnormalities or received a concomitant medication that could increase the risk of developing QTc prolongation. The risk factors for congenital long QT syndrome, cardiovascular disease, or electrolyte abnormalities were more common in older patients. This analysis emphasizes the importance of individualized benefit/ risk assessment during treatment decisions, especially when considering drugs with known or possible QTc prolongation risk.

show abstract

Section: Risk Factormentioning

confidence: 88%

Risk Factors of QTc Prolongation in Women With Hormone Receptor‒positive/Human Epidermal Growth Factor Receptor 2‒negative Metastatic Breast Cancer: A Retrospective Analysis of Health Care Claims Data

Ward

Harnett

Bell

et al. 2019

Clinical Therapeutics

View full text Add to dashboard Cite

show abstract

“…Disproportionality for neurologic irAE reporting as a function of variable ICI regimen was estimated by calculating the ROR Chi-square (Graphpad Prism 7), described elsewhere and detailed in Additional file 1: Table S2 [ [20][21][22]. The lower end of ROR 95% confidence interval (CI) ≥1 is the threshold used for significant statistical signal detection.…”

Section: Discussionmentioning

confidence: 99%

Neurologic toxicity associated with immune checkpoint inhibitors: a pharmacovigilance study

Johnson¹,

Manouchehri²,

Haugh³

et al. 2019

j. immunotherapy cancer

Self Cite

263

257

View full text Add to dashboard Cite

Background: Immune checkpoint inhibitors (ICI) produce durable antitumor responses but provoke autoimmune toxicities, including uncommon but potentially devastating neurologic toxicities. The clinical features, including the spectrum, timing, and outcomes, of ICI-induced neurologic toxicities are not well characterized. Methods: We performed disproportionality analysis using Vigibase, the World Health Organization pharmacovigilance database, comparing neurologic adverse event (AE) reporting in patients receiving ICIs vs. the full database. Neurologic AEs were classified by group queries using Medical Dictionary for Regulatory Activities, between database inception to September 28, 2018. Associations between ICIs and neurologic AEs were assessed using reporting odds ratios (ROR) and information component (IC). IC compares observed and expected values to find associations between drugs and AEs using disproportionate Bayesian reporting; IC 025 (lower end of the IC 95% credibility interval) > 0 is considered statistically significant. Results: Among the full database, 18,518,994 AEs were reported, including 48,653 with ICIs. ICIs were associated with higher incidence of myasthenia gravis (0.47% of ICI reports vs. 0.04% of the full database, ROR 16.5 [95% CI 14. 5-18.9]; IC 025 3.31), encephalitis (0.51% vs. 0.05%, ROR 10.4 [95% CI 9.2-11.8]; IC 025 3.15), peripheral neuropathy (1. 16% vs. 0.67%, IC 025 0.68), and meningitis (0.15% vs. 0.06%, ROR 3.1 [95% CI 2.5-3.9]; IC 025 1.01). Myasthenia gravis and encephalitis were associated with anti-PD-1 whereas other neurologic AEs were associated with anti-CTLA-4. Myasthenia gravis was characterized by high fatality rates (~20%), early onset (median 29 days), and frequent concurrent myocarditis and myositis; whereas other neurologic AEs had lower fatality rates (6-12%), later onset (median 61-80 days), and were non-overlapping. Conclusions: ICIs produce a spectrum of distinct classes of neurologic AEs that can cause significant morbidity and mortality and tend to occur early and with class-specific associations.

show abstract

“…(16,17) As compared to Bayesian statistics, disproportionality in VigiBase can also be assessed using a more classical frequentist approach by calculating the ROR Chi 2 , described and used elsewhere (Supplemental Table-2). (13,(18)(19)(20)(21) The lower end of ROR 95% confidence interval (CI)≥1 is the threshold deemed significant. ROR was calculated taking as comparator the entire database since 2013 to provide a contemporary control group for ibrutinib (first ICSR in VigiBase in 2013, the year of its first FDA approval).…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular Toxicities Associated With Ibrutinib

Salem

Manouchehri

Bretagne

et al. 2019

Journal of the American College of Cardiology

Self Cite

195

173

View full text Add to dashboard Cite

Background: Ibrutinib has revolutionized treatment for several B-cell malignancies. However, a recent clinical trial where ibrutinib was used in front-line setting showed increased mortality during treatment compared to conventional chemotherapy. Cardiovascular toxicities were suspected as the culprit but not directed assessed in the study. Objective: We aimed to identify and characterize cardiovascular adverse drug reactions (CV-ADR) associated with ibrutinib. Methods: We utilized VigiBase (International pharmacovigilance database) and performed a disproportionality analysis using reporting odds-ratios (ROR) and information component (IC) to determine whether CV-ADR and CV-ADR deaths were associated with ibrutinib. IC compares observed and expected values to find associations between drugs and ADR using disproportionate Bayesianreporting; IC025 (lower end of the IC 95% credibility interval)> 0 is significant. Results: We identified 303 ibrutinib-associated cardiovascular deaths. Ibrutinib was associated with

show abstract

Increased long QT and torsade de pointes reporting on tamoxifen compared with aromatase inhibitors

Cited by 43 publications

References 25 publications

Risk Factors of QTc Prolongation in Women With Hormone Receptor‒positive/Human Epidermal Growth Factor Receptor 2‒negative Metastatic Breast Cancer: A Retrospective Analysis of Health Care Claims Data

Risk Factors of QTc Prolongation in Women With Hormone Receptor‒positive/Human Epidermal Growth Factor Receptor 2‒negative Metastatic Breast Cancer: A Retrospective Analysis of Health Care Claims Data

Neurologic toxicity associated with immune checkpoint inhibitors: a pharmacovigilance study

Cardiovascular Toxicities Associated With Ibrutinib

Contact Info

Product

Resources

About