SEARCHOTHERoncology, gastroenterology

other·oncology, gastroenterology, neurology, clinical trial, research methods·PMC10046586

Neuropsychiatric Adverse Drug Reactions with Tyrosine Kinase Inhibitors in Gastrointestinal Stromal Tumors: An Analysis from the European Spontaneous Adverse Event Reporting System

Cancers · 8 authors, 2 centres

AI SUMMARY

FIDELITY 100%

POPULATIONPatients with gastrointestinal stromal tumors treated with tyrosine kinase inhibitors (imatinib, sunitinib, avapritinib, regorafenib, or ripretinib)

INTERVENTIONNeuropsychiatric adverse drug reactions associated with each tyrosine kinase inhibitor

COMPARISONDisproportionality analysis comparing each tyrosine kinase inhibitor against all others combined

This summary was generated by AI from a single paper. It has not been reviewed by a clinician and is not clinical advice. Verify against the source before acting on it.

AGENT 01 · STRUCTURED SUMMARY

TRACE TO SOURCE

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TL;DR

Neuropsychiatric adverse drug reactions were reported in 17.8% of cases, with avapritinib showing a significantly higher reporting probability compared to other tyrosine kinase inhibitors, including previously unreported adverse reactions such as hallucinations and olfactory nerve disorders.

Full summary

897 CHARS

This study analyzed individual case safety reports (ICSRs) collected in the European EudraVigilance database up to 31 December 2021 for five tyrosine kinase inhibitors approved for gastrointestinal stromal tumors. Neuropsychiatric adverse drug reactions were reported in 1511 ICSRs (17.8%), predominantly in males and adult patients. Avapritinib showed a higher reporting probability of neuropsychiatric adverse drug reactions compared to other tyrosine kinase inhibitors, with significantly elevated reporting odds ratios for hallucinations, olfactory nerve disorders, and lumbar spinal cord and nerve root disorders. Regorafenib showed an increased frequency of cerebral infarction, and ripretinib showed higher disturbances in consciousness. The authors concluded that further studies are needed to characterize the neuropsychiatric safety profiles of newly approved tyrosine kinase inhibitors.

PICO

PPOPULATION

Patients with gastrointestinal stromal tumors treated with tyrosine kinase inhibitors (imatinib, sunitinib, avapritinib, regorafenib, or ripretinib)

IINTERVENTION

Neuropsychiatric adverse drug reactions associated with each tyrosine kinase inhibitor

OOUTCOME

Reporting frequency and reporting odds ratios of neuropsychiatric adverse drug reactions

STUDY TYPE

other

SPECIALTY

oncology

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10046586

Neuropsychiatric Adverse Drug Reactions with Tyrosine Kinase Inhibitors in Gastrointestinal Stromal Tumors: An Analysis from the European Spontaneous Adverse Event Reporting System

Cancers

READ THE FULL PAPER

ABSTRACT

Simple Summary Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms arising in the gastrointestinal tract, especially in the stomach (60–65%). The development of most cases of GISTs is associated with activating mutations in the receptor tyrosine kinase genes KIT and PDGFRA. The discovery of mutations leads to the approval of tyrosine kinase inhibitors (TKIs) for GISTs. Considering the recent approval of the last two TKIs and given their increased use in clinical practice, a spontaneous reporting system (SRS) database, the main tool in pharmacovigilance, takes a remarkable role in promptly characterizing the benefit/risk profile of these new drugs and consequently improve the quality of life of patients affected by GISTs. Abstract Tyrosine kinase inhibitors (TKIs) are widely used in gastrointestinal stromal tumors (GISTs). The aim of this study is to evaluate the reporting frequency of neuropsychiatric adverse drug reactions (ADRs) for TKIs through the analysis of European individual case safety reports (ICSRs). All ICSRs collected in EudraVigilance up to 31 December 2021 with one TKI having GISTs as an indication (imatinib (IM), sunitinib (SU), avapritinib (AVA), regorafenib (REG), and ripretinib (RIP)) were included. A disproportionality analysis was performed to assess the frequency of reporting for each TKI compared to all other TKIs. The number of analyzed ICSRs was 8512, of which 57.9% were related to IM. Neuropsychiatric ADRs were reported at least once in 1511 ICSRs (17.8%). A higher reporting probability of neuropsychiatric ADRs was shown for AVA. Most neuropsychiatric ADRs were known, except for a higher frequency of lumbar spinal cord and nerve root disorders (reporting odds ratio, ROR 4.46; confidence interval, CI 95% 1.58–12.54), olfactory nerve disorders (8.02; 2.44–26.33), and hallucinations (22.96; 8.45–62.36) for AVA. The analyses of European ICSRs largely confirmed the safety profiles of TKIs in GISTs, but some ADRs are worthy of discussion. Further studies are needed to increase the knowledge of the neuropsychiatric disorders of newly approved TKIs.

CITATION EXPORT

Maria Antonietta Barbieri, Emanuela Elisa Sorbara, Giulia Russo et al.. Neuropsychiatric Adverse Drug Reactions with Tyrosine Kinase Inhibitors in Gastrointestinal Stromal Tumors: An Analysis from the European Spontaneous Adverse Event Reporting System. Cancers. (2023). https://doi.org/10.3390/cancers15061851

AUTHORS

8 · 2 CENTRES

Maria Antonietta Barbieri, Emanuela Elisa Sorbara, Giulia Russo, Giuseppe Cicala, Tindara Franchina, Mariacarmela Santarpia, Nicola Silvestris, Edoardo Spina

1Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy
2Department of Human Pathology in Adulthood and Childhood Gaetano Barresi, University of Messina, 98125 Messina, Italy

EDITOR / REVIEWER

Daruka Mahadevan