Abstract 427P
Background
Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI) represent an important treatment option in ALKpositive non-small cell lung cancer. The 5 approved ALK TKIs differ in their efficacy and safety profile. Thus, we conducted an analysis of selected adverse events (AE) of ALK TKIs, reported in the pharmacovigilance database EudraVigilance (EV).
Methods
The EV data from Jan 2012 through Dec 2023 was searched. Reports on crizotinib, ceritinib, alectinib, brigatinib and lorlatinib were filtered. Selected AEs, listed in the “Specialwarnings and precautions for use” of the Summaries of Product Characteristics, were identified. Reports were categorized per Medical Dictionary for Regulatory Activities (MedDRA v25.1). Disproportionality analyses were conducted to detect safety signals by calculating reporting odds ratios (RORs), considered as statistically significant if the ROR lower limit of the 95% confidence interval was >1. Only safety signals with a ROR >2 are reported.
Results
During 2012–2023, 3377 reports of suspected AEs were reported in the EV database for crizotinib (1365), alectinib (1069), lorlatinib (470), ceritinib (246) and brigatinib (227). Significant safety signs were found for general AEs: diarrhea, nausea and vomiting were significantly associated with ceritinib (ROR 4.81), renal and urinary disorders with crizotinib (ROR 2.42), whereas musculoskeletal or connective tissue disorders and pneumonitis were significantly associated with alectinib (ROR 3.38 and ROR 2.08, respectively). Also, significant safety signs were found for specific AEs: eye disorders were significantly associated with crizotinib (ROR 3.19), hyperglycaemia with ceritinib (ROR 4.04), hypertension with brigatinib (ROR 16.87), hyperlipidemia and psychiatric disorders with lorlatinib (ROR 79.05, and ROR 3.11, respectively). Photosensitivity was associated both with alectinib (ROR 2.29) and brigatinib (ROR 8.16).
Conclusions
Our analysis of postmarketing safety data of ALK TKIs found numerous safety signals that confirm the variability in their safety profiles. These data can aid the selection of ALK TKIs in routine clinical practice.
Legal entity responsible for the study
The authors.
Funding
This work was financially supported by the Slovenian Research Agency, Grant No. P1-0189 and P3-0360.
Disclosure
L. Knez: Financial Interests, Personal, Invited Speaker: Roche, MSD; Financial Interests, Institutional, Other, Educational projects within employment at the University of Ljubljana, Faculty of Pharmacy: Swixx, Krka; Financial Interests, Institutional, Other, Research projects within employment at the University of Ljubljana, Faculty of Pharmacy: AstraZeneca. T. Jugovic: Other, Personal, Full or part-time Employment: Lek Pharmaceuticals (Sandoz). N. Cebron Lipovec: Financial Interests, Institutional, Other: Swixx, Pharmalinea, Krka; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Invited Speaker: Mediately.