Lorlatinib – Induced pulmonary arterial hypertension
Section snippets
Case 1
A 55-year-old woman had previously been treated with various chemotherapies for a metastatic NSCLC from 2010 to December 2014. Then she received crizonitib and ceretinib because of tumor progression, as her NSLC expressed ALK rearrangement. A progression on ceretinib led to starting lorlanitib 50 mg bid in August, 2017.
One month later, she complained of rapidly progressive NYHA functional class IV dyspnea. She was unable to perform a walk test. Echocardiography estimated systolic pulmonary
Case 2
A 64-year-old male patient exhibited metastatic NSCLC with ALK rearrangement had been successively treated with crizonitib, ceretinib then lorlanitib 50 mg bid, because of uncontrolled disease.
Two months after lorlatinib introduction, he complained of a dramatically increasing afebrile dyspnea (in NYHA functional class III). He walked 368 m with oxygenotherapy at 5 L/min in a 6 min walk test. Systolic pulmonary arterial pressure on echocardiography was estimated at 62 mmHg with apparent normal
Acknowledgement
We acknowledge the French pulmonary hypertension pharmacovigilance network, VIGIAPATH, supported by the Agence Nationale de Sécurité du Médicament et des Produits de Santé (ANSM).
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Pharmacology and pharmacovigilance of protein kinase inhibitors
2022, TherapiesCitation Excerpt :More recently, several cases have been reported of potential association with or deterioration of pre-existing PAH with other PKIs such as bosutinib, ponatinib and lapatinib [13]. Although the underlying mechanism of dasatinib related PAH is still unclear, evidence suggests that SRC and SRC-independent mechanisms (through mitochondrial ROS production) are implicated [47–52]. A pharmacodynamics-pharmacovigilance study correlating affinities of PKI for a range of protein kinases and disproportionality values highlighted a possible role of SRC protein kinases as well as other targets, such as TEC whose role remains to be determined [13].
Postmarketing safety of anaplastic lymphoma kinase (ALK) inhibitors: an analysis of the FDA Adverse Event Reporting System (FAERS)
2021, ESMO OpenCitation Excerpt :Treatment with ALK inhibitors is usually well tolerated; however, there are common class adverse events such as nausea, vomiting, diarrhea, pneumonitis, and cardiac toxicity.12 Some less common adverse events have been reported as well including rectal perforation,13 cataract, macular edema or blindness,14,15 osteitis,16 ventricular fibrillation,17,18 pulmonary arterial hypertension,19 pancreatitis,20 cholestasis,21 alopecia,22 proteinuria,23 myasthenia gravis,24 toxic epidermal necrolysis,25 sarcoid-like reaction,26 and photosensitivity.27 Treatment discontinuation due to adverse events among different ALK inhibitors were as follow: 12% with crizotinib as in the PROFILE 1014 trial,28 5% with ceritinib as in the ASCEND 4 trial,29 11% with alectinib as in the ALEX trial,30 12% with brigatinib as in the ALTA-1L trial,10 and 7% with lorlatinib as in the CROWN trial.31
Pulmonary Arterial Hypertension in ALK Receptor Tyrosine Kinase–Positive Lung Cancer Patient: Adverse Event or Disease Spread?
2019, Journal of Thoracic OncologyNovel Pharmacological Targets for Pulmonary Arterial Hypertension
2021, Comprehensive Physiology
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Thses authors are equal contribution as first authors.