PMID- 34528216 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220224 IS - 2199-1154 (Print) IS - 2198-9788 (Electronic) IS - 2198-9788 (Linking) VI - 9 IP - 1 DP - 2022 Mar TI - Adverse Drug Reactions with HER2-Positive Breast Cancer Treatment: An Analysis from the Italian Pharmacovigilance Database. PG - 91-107 LID - 10.1007/s40801-021-00278-z [doi] AB - BACKGROUND: Anti-HER2 therapy has evolved in the last years and an important role in this transformation was that of monoclonal antibodies and tyrosine kinase inhibitors. Considering their extended use in clinical practice, some toxicity problems have been highlighted around these drugs. OBJECTIVE: To analyze the onset of adverse drug reactions (ADRs) related to the use of HER2-positive breast cancer treatments through a spontaneous reporting system (SRS) database. METHODS: All ADR reports having as suspected drug trastuzumab, pertuzumab, lapatinib, or trastuzumab emtansine (TDM-1), 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 2020 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 the serious ADR reports collected in Sicily, focusing on type of seriousness, age, sex, concomitant drugs, comorbidities, time to onset (TTO), and time to resolution (TTR). RESULTS: Of the 3609 Italian reports, 65.6% were related to trastuzumab (n = 2367), followed by pertuzumab, TDM-1, and lapatinib. Almost all reports occurred in female patients (94.3%) and were most frequent in the age group 18-65 years (69.6%). A higher number of cases were related to general disorders and administration site conditions (n = 1079; 29.9%), gastrointestinal disorders (n = 1037; 28.7%), skin disorders (n = 821; 22.7%), and blood disorders (n = 599; 16.6%). Cases involving trastuzumab and pertuzumab mainly reported general disorders (n = 788; 33.3% and n = 194; 32.1%, respectively) while more than half of the reports associated with lapatinib were related to gastrointestinal (n = 184; 59.7%) and skin diseases (n = 146; 47.4%). Regarding TDM-1, 40% of reports had at least one ADR belonging to blood and lymphatic system disorders. The case-by-case assessment of Sicilian ADR reports showed that 40 cases were serious (33.3%), with a median TTO of 37 (6-97) days. Serious ADR reports mainly involved the onset of thrombocytopenia (n = 8; 20.0%), diarrhea (n = 6; 15.0%), asthenia and cardiac failure (both with n = 5; 12.5%), vomiting, hypersensitivity, and ejection fraction decreased (all with n = 4; 10.0%) and stomatitis (n = 3: 7.5%). CONCLUSION: This study is fundamentally consistent with results from the literature. Given the serious clinical condition of breast cancer and taking into account the importance of preventing some clinically relevant ADRs related to the use of anti-HER2 therapy, further analyses are essential to better describe the safety profile of these target therapies. CI - (c) 2021. The Author(s). FAU - Barbieri, Maria Antonietta AU - Barbieri MA AUID- ORCID: 0000-0002-2019-4696 AD - Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. FAU - Sorbara, Emanuela Elisa AU - Sorbara EE AUID- ORCID: 0000-0002-2447-8610 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 Adult and Developmental Human Pathology "Gaetano Barresi", University of Messina, Messina, Italy. FAU - Spina, Edoardo AU - Spina E AUID- ORCID: 0000-0002-2509-7449 AD - Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. espina@unime.it. LA - eng PT - Journal Article DEP - 20210915 PL - Switzerland TA - Drugs Real World Outcomes JT - Drugs - real world outcomes JID - 101658456 PMC - PMC8844323 COIS- Maria Antonietta Barbieri, Emanuela Elisa Sorbara, Giuseppe Cicala, Vincenza Santoro, Paola Maria Cutroneo, Tindara Franchina, and Edoardo Spina have no conflicts of interest that are relevant to the content of this article. The research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/09/17 06:00 MHDA- 2021/09/17 06:01 PMCR- 2021/09/15 CRDT- 2021/09/16 07:30 PHST- 2021/08/23 00:00 [accepted] PHST- 2021/09/17 06:00 [pubmed] PHST- 2021/09/17 06:01 [medline] PHST- 2021/09/16 07:30 [entrez] PHST- 2021/09/15 00:00 [pmc-release] AID - 10.1007/s40801-021-00278-z [pii] AID - 278 [pii] AID - 10.1007/s40801-021-00278-z [doi] PST - ppublish SO - Drugs Real World Outcomes. 2022 Mar;9(1):91-107. doi: 10.1007/s40801-021-00278-z. Epub 2021 Sep 15.