Effect of small angiokinase inhibitor nintedanib (BIBF 1120) on QT interval in patients with previously untreated, advanced renal cell cancer in an open-label, phase II study

Eisen, Tim; Shparyk, Yaroslav; MacLeod, Nicholas; Jones, Robert J.; Wallenstein, Gudrun; Temple, Graham; Khder, Yasser; Dallinger, Claudia; Studeny, Matus; Loembé, Arsene-Bienvenu; Bondarenko, Igor

doi:10.1007/s10637-013-9962-7

Cited by 51 publications

(52 citation statements)

References 31 publications

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“…Nintedanib showed dose-proportional increases in C max and AUC over a dosage range of 50-450 mg once daily and 150-300 mg twice daily [52]. There was only slight accumulation of nintedanib following multiple twice-daily dosing [61], and interpatient variability for all pharmacokinetics parameters was moderate to high [51,52,61], in line with Phase I studies of other TKIs [62][63][64].…”

Section: Clinical Pharmacokineticssupporting

confidence: 74%

Discovery and Development of Nintedanib: A Novel Antiangiogenic and Antifibrotic Agent

Roth¹,

Binder²,

Colbatzky³

et al. 2016

Successful Drug Discovery

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Section: Clinical Pharmacokineticssupporting

confidence: 74%

Discovery and Development of Nintedanib: A Novel Antiangiogenic and Antifibrotic Agent

Roth¹,

Binder²,

Colbatzky³

et al. 2016

Successful Drug Discovery

Self Cite

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“…There was also no evidence of QT-prolongation with nintedanib treatment in INPULSIS or TOMORROW (pooled data; nintedanib: n = 723, placebo: n = 508). This finding is further supported by an oncology study of nintedanib in renal cell carcino ma patients ( n = 64), which also reported no evidence of clinically relevant QT-prolongation or drug-related cardiovascular events at a higher dose of 200 mg bid [34]. …”

Section: Nintedanib Use In Patients With Additional Risk Factorsmentioning

confidence: 67%

Nintedanib in Idiopathic Pulmonary Fibrosis: Practical Management Recommendations for Potential Adverse Events

et al. 2018

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Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with a dismal survival rate of only 3 years and no curative pharmacological therapy. The recent approval of 2 anti-fibrotic drugs (nintedanib and pirfenidone) that slow disease progression has provided some hope for patients. However, effectively managing anti-fibrotic treatment can be a challenge due to tolerability issues, the presence of pulmonary and extra-pulmonary comorbidities, and the need for concomitant medications in many patients. In general, making clear evidence-based decisions can be difficult for physicians because patients with comorbidities are often excluded from clinical trials. Since currently anti-fibrotic drugs are the only effective therapeutics capable of slowing disease progression, it is imperative that all treatment options are thoroughly evaluated and exhausted in each individual, irrespective of complicating factors, to permit the best outcome for the patient. In this review, we present data from clinical trials, post hoc analyses, post-marketing surveillance, and real-world studies that are relevant to the management of nintedanib treatment. In addition, we also provide practical recommendations developed by a multidisciplinary panel of experts for the management of nintedanib treatment in patients with IPF associated complications and those experiencing gastrointestinal side effects.

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“…QTc prolongation was common (37%) in patients with hepatic impairment treated with bosutinib,10 but this was not seen in other smaller studies 11, 12. QTc prolongation was infrequent or absent with afatinib, crizotinib, ceritinib, dovitinib, imatinib, lapatinib, lenvatinib, nintedanib, pazopanib, and ponatinib 9, 14, 16, 17, 19, 24, 26, 27, 29, 30, 31, 32, 33, 35, 36, 38, 39, 72, 78, 81, 161, 162, 163, 164…”

Section: Resultsmentioning

confidence: 97%

Incidence, Diagnosis, and Management of QT Prolongation Induced by Cancer Therapies: A Systematic Review

Porta‐Sánchez

Gilbert

Spears

et al. 2017

JAHA

159

142

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BackgroundThe cardiovascular complications of cancer therapeutics are the focus of the burgeoning field of cardio‐oncology. A common challenge in this field is the impact of cancer drugs on cardiac repolarization (ie, QT prolongation) and the potential risk for the life‐threatening arrhythmia torsades de pointes. Although QT prolongation is not a perfect marker of arrhythmia risk, this has become a primary safety metric among oncologists. Cardiologists caring for patients receiving cancer treatment should become familiar with the drugs associated with QT prolongation, its incidence, and appropriate management strategies to provide meaningful consultation in this complex clinical scenario.Methods and ResultsIn this article, we performed a systematic review (using Preferred Reporting Items of Systematic Reviews and Meta‐Analyses (PRISMA) guidelines) of commonly used cancer drugs to determine the incidence of QT prolongation and clinically relevant arrhythmias. We calculated summary estimates of the incidence of all and clinically relevant QT prolongation as well as arrhythmias and sudden cardiac death. We then describe strategies to prevent, identify, and manage QT prolongation in patients receiving cancer therapy. We identified a total of 173 relevant publications. The weighted incidence of any corrected QT (QTc) prolongation in our systematic review in patients treated with conventional therapies (eg, anthracyclines) ranged from 0% to 22%, although QTc >500 ms, arrhythmias, or sudden cardiac death was extremely rare. The risk of QTc prolongation with targeted therapies (eg, small molecular tyrosine kinase inhibitors) ranged between 0% and 22.7% with severe prolongation (QTc >500 ms) reported in 0% to 5.2% of the patients. Arrhythmias and sudden cardiac death were rare.ConclusionsOur systematic review demonstrates that there is variability in the incidence of QTc prolongation of various cancer drugs; however, the clinical consequence, as defined by arrhythmias or sudden cardiac death, remains rare.

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Effect of small angiokinase inhibitor nintedanib (BIBF 1120) on QT interval in patients with previously untreated, advanced renal cell cancer in an open-label, phase II study

Abstract: Nintedanib administered at 200 mg twice daily was not associated with clinically relevant QT prolongation.

Cited by 51 publications

References 31 publications

Discovery and Development of Nintedanib: A Novel Antiangiogenic and Antifibrotic Agent

Discovery and Development of Nintedanib: A Novel Antiangiogenic and Antifibrotic Agent

Nintedanib in Idiopathic Pulmonary Fibrosis: Practical Management Recommendations for Potential Adverse Events

Incidence, Diagnosis, and Management of QT Prolongation Induced by Cancer Therapies: A Systematic Review

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