ceritinib and Pericarditis

Recently, cases of cardiovascular toxicities, such as pericarditis, caused by anaplastic lymphoma kinase (ALK) inhibitors have been reported; however, whether these adverse events are common among all ALK inhibitors remains unclear.. This study aimed to clarify the cardiovascular toxicity profile of ALK inhibitors using an adverse event spontaneous report database.. We analyzed data from VigiBase, the WHO global database of individual safety reports, from its inception in 1968 to December 2021. We calculated the reporting odds ratio to evaluate the association between ALK inhibitors (crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib) and 21 cardiovascular adverse events. Time to onset of pericarditis from ALK inhibitor administration was analyzed.. Of the 27,994,584 reports, 19,911 involved treatment with ALK inhibitors. Among the 21 cardiovascular toxicities, only pericarditis signals were detected with all five ALK inhibitors (crizotinib [reporting odds ratios (ROR), 4.7; 95% CI 3.63-6.15], ceritinib [ROR, 12.9; 95% CI 9.37-17.79], alectinib [ROR, 4.8; 95% CI 3.15-7.42], brigatinib [ROR, 3.5; 95% CI 1.33-9.46], and lorlatinib [ROR, 6.4; 95% CI 3.60-11.22]). For torsade de pointes/QT prolongation, signals were detected with crizotinib (ROR, 5.0; 95% CI 3.72-6.77) and ceritinib (ROR, 4.2; 95% CI 2.17-8.05), whereas for hypertension, they were identified only with brigatinib (ROR, 3.9; 95% CI 2.88-5.20), and for heart failure, they were detected with alectinib (ROR, 2.2; 95% CI 1.60-2.90), crizotinib (ROR, 2.1; 95% CI 1.72-2.48), and lorlatinib (ROR, 2.0; 95% CI 1.27-3.23). Regarding time-to-onset analysis from drug administration to adverse event reporting, for pericarditis, it ranged from 52.5 days for alectinib to 166.5 days for crizotinib.. Systematic evaluation of ALK inhibitor-associated adverse events revealed differences in the cardiotoxicity profiles among ALK inhibitors. Understanding the differences in the cardiovascular toxicity profile of each ALK inhibitor will contribute to safe drug therapy when switching between ALK inhibitors.

Topics: Anaplastic Lymphoma Kinase; Carcinoma, Non-Small-Cell Lung; Crizotinib; Humans; Lung Neoplasms; Pericarditis; Pharmacovigilance; Protein Kinase Inhibitors; World Health Organization

Tyrosine kinase inhibitors are now major actors for the treatment of non-small-cell metastatic lung cancers where ROS 1 gene rearrangement is present. Because of the rapid development of these new therapies, developing information about their monitoring and knowledge about their potential toxicities is essential. We describe the case of a patient who was treated with ceritinib as a third line approach for a metastatic lung adenocarcinoma with ROS1 rearrangement. After two months, the patient developed acute respiratory distress with pericarditis and pleurisy. A hypersensitivity reaction was suggested and supported by favorable clinical and radiological outcomes within three days following ceritinib discontinuation and systemic corticosteroid introduction. Pleural effusion, pericarditis and diffuse pulmonary infiltration associated to ceritinib have not often been described previously. Despite few data of pulmonary toxicity related to ceritinib, the current observation highlights the need for caution and regular monitoring when using these inhibitors.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cardiotoxicity; Drug Hypersensitivity; Female; Humans; Lung Diseases, Interstitial; Lung Neoplasms; Neoplasm Metastasis; Pericarditis; Pleural Effusion; Pyrimidines; Respiratory Distress Syndrome; Sulfones