PMID- 36505840
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230109
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 12
DP  - 2022
TI  - Safety profile of tyrosine kinase inhibitors used in non-small-cell lung cancer: 
      An analysis from the Italian pharmacovigilance database.
PG  - 1005626
LID - 10.3389/fonc.2022.1005626 [doi]
LID - 1005626
AB  - INTRODUCTION: Non-small cell lung cancer (NSCLC) is often caused by molecular 
      alterations that can be detected by predictive biomarkers including mutations or 
      amplifications of several genes. Several tyrosine kinase inhibitors (TKIs) have 
      been approved in Europe by the European Medicines Agency (EMA) for NSCLC. The aim 
      of this study was to analyze the onset of adverse drug reactions (ADRs) related 
      to TKIs in NSCLC through a spontaneous reporting system (SRS) database. METHODS: 
      All ADR reports having as suspected drug afatinib (AFT), alectinib (ALEC), 
      brigatinib (BRG), ceritinib (CER), crizotinib (CRIZ), erlotinib (ERL), gefitinib 
      (GEF), lorlatinib (LORL), nintedanib (NTB), and osimertinib (OSI) recorded into 
      the Report Reazioni Avverse dei Medicinali (RAM) system database for national 
      data and into the Italian SRS database for Sicilian data and collected from 2006 
      to 2021 have been evaluated. A descriptive analysis of basal demographic and 
      drug-related characteristics was performed. A case-by-case methodology was 
      conducted paying particular attention to all serious ADR reports collected in 
      Sicily, focusing on type of seriousness, age, sex, concomitant drugs, and 
      comorbidities. RESULTS: Of the 3,048 Italian reports, most of ADRs were related 
      to ERL (n = 1,448), followed by AFT (n = 435) and GEF (n = 366). ADR reports were 
      slightly more frequent in females (52.2%) and in the age group >65 years (53.0%). 
      A higher number of cases were related to skin disorders (n = 1,766; 57.9%), 
      followed by gastrointestinal disorders (n = 1,024; 33.6%), general disorders and 
      administration site conditions (n = 536; 17.6%), and infections (n = 483; 15.8%). 
      The case-by-case assessment of Sicilian ADRs showed that 33 cases were serious 
      (12.5%) and mainly involved ERL (n = 17; 51.5%), occurring in males with a higher 
      onset of respiratory diseases (30.3%) such as respiratory failure, interstitial 
      lung disease and dyspnea. DISCUSSION: The analysis of spontaneous ADR reports of 
      TKIs confirmed, in general, well-known risks, which often include skin, 
      gastrointestinal, general, liver, and respiratory diseases as well as infections. 
      However, more attention should be paid to the occurrence of serious 
      life-threatening ADRs including respiratory failure, interstitial lung disease, 
      and cardiogenic shock, especially in young patients.
CI  - Copyright (c) 2022 Barbieri, Sorbara, Cicala, Santoro, Cutroneo, Franchina, 
      Santarpia, Silvestris and Spina.
FAU - Barbieri, Maria Antonietta
AU  - Barbieri MA
AD  - Department of Clinical and Experimental Medicine, University of Messina, Messina, 
      Italy.
FAU - Sorbara, Emanuela Elisa
AU  - Sorbara EE
AD  - Department of Clinical and Experimental Medicine, University of Messina, Messina, 
      Italy.
FAU - Cicala, Giuseppe
AU  - Cicala G
AD  - Department of Clinical and Experimental Medicine, University of Messina, Messina, 
      Italy.
FAU - Santoro, Vincenza
AU  - Santoro V
AD  - Department of Clinical and Experimental Medicine, University of Messina, Messina, 
      Italy.
FAU - Cutroneo, Paola Maria
AU  - Cutroneo PM
AD  - Sicilian Regional Pharmacovigilance Centre, University Hospital of Messina, 
      Messina, Italy.
FAU - Franchina, Tindara
AU  - Franchina T
AD  - Department of Human Pathology in Adulthood and Childhood Gaetano Barresi, 
      University of Messina, Messina, Italy.
FAU - Santarpia, Mariacarmela
AU  - Santarpia M
AD  - Department of Human Pathology in Adulthood and Childhood Gaetano Barresi, 
      University of Messina, Messina, Italy.
FAU - Silvestris, Nicola
AU  - Silvestris N
AD  - Department of Human Pathology in Adulthood and Childhood Gaetano Barresi, 
      University of Messina, Messina, Italy.
FAU - Spina, Edoardo
AU  - Spina E
AD  - Department of Clinical and Experimental Medicine, University of Messina, Messina, 
      Italy.
LA  - eng
PT  - Journal Article
DEP - 20221123
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC9727240
OTO - NOTNLM
OT  - adverse drug reactions
OT  - anaplastic lymphoma kinase
OT  - epidermal growth factor receptor
OT  - non-small cell lung cancer
OT  - pharmacovigilance
OT  - tyrosine kinase inhibitors
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/12/13 06:00
MHDA- 2022/12/13 06:01
PMCR- 2022/01/01
CRDT- 2022/12/12 11:06
PHST- 2022/07/28 00:00 [received]
PHST- 2022/11/03 00:00 [accepted]
PHST- 2022/12/12 11:06 [entrez]
PHST- 2022/12/13 06:00 [pubmed]
PHST- 2022/12/13 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2022.1005626 [doi]
PST - epublish
SO  - Front Oncol. 2022 Nov 23;12:1005626. doi: 10.3389/fonc.2022.1005626. eCollection 
      2022.