{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:31:49Z","timestamp":1760149909338,"version":"build-2065373602"},"reference-count":46,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T00:00:00Z","timestamp":1695340800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"national funds from Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["UIDB\/00709\/2020","UIDP\/00709\/2020"],"award-info":[{"award-number":["UIDB\/00709\/2020","UIDP\/00709\/2020"]}]},{"name":"Fundo Europeu de Desenvolvimento Regional (FEDER) under the scope of PORTUGAL 2020 and Programa Operacional do Centro (CENTRO 2020)","award":["UIDB\/00709\/2020","UIDP\/00709\/2020"],"award-info":[{"award-number":["UIDB\/00709\/2020","UIDP\/00709\/2020"]}]},{"name":"Portuguese National Authority of Medicines and Health Products I.P. (INFARMED)","award":["UIDB\/00709\/2020","UIDP\/00709\/2020"],"award-info":[{"award-number":["UIDB\/00709\/2020","UIDP\/00709\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Cyclin-dependent kinases 4 and 6 (CDK4\/6) inhibitors are a recent targeted therapy approved for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2\u2212) advanced breast cancer. Abemaciclib, palbociclib and ribociclib demonstrated great efficacy and safety during clinical studies. However, differences in their adverse-event profiles have been observed. This work aims to describe the suspected adverse drug reactions (ADRs), such as leukopenia and thrombocytopenia, reported for each CDK4\/6 inhibitor in the EudraVigilance (EV) database. Data on individual case safety reports (ICSRs) were obtained by accessing the European spontaneous reporting system via the EV website. Information on concomitant drug therapy, including fulvestrant, letrozole, anastrozole and exemestane, was also analyzed. A total of 1611 ICSRs were collected from the EV database. Most reports of palbociclib and ribociclib were classified as serious cases for both suspected leukopenia and thrombocytopenia ADRs. However, most patients had their leukopenia and thrombocytopenia recovered\/resolved. On the contrary, reports of abemaciclib were mostly characterized as non-serious cases. Abemaciclib and palbociclib were often combined with fulvestrant, while ribociclib was generally associated with letrozole. Pharmacovigilance studies are crucial for the early identification of potential ADRs and to better differentiate the toxicity profile of the different CDK4\/6 inhibitors, particularly in a real-world setting.<\/jats:p>","DOI":"10.3390\/ph16101340","type":"journal-article","created":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T10:36:26Z","timestamp":1695551786000},"page":"1340","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Hematological Events Potentially Associated with CDK4\/6 Inhibitors: An Analysis from the European Spontaneous Adverse Event Reporting System"],"prefix":"10.3390","volume":"16","author":[{"given":"Vera","family":"Martins","sequence":"first","affiliation":[{"name":"Health Sciences Faculty, University of Beira Interior (FCS-UBI), 6200-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3332-7280","authenticated-orcid":false,"given":"Mafalda","family":"Jesus","sequence":"additional","affiliation":[{"name":"Health Sciences Faculty, University of Beira Interior (FCS-UBI), 6200-506 Covilh\u00e3, Portugal"},{"name":"Health Sciences Research Centre, University of Beira Interior (CICS-UBI), 6200-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9068-4607","authenticated-orcid":false,"given":"Lu\u00edsa","family":"Pereira","sequence":"additional","affiliation":[{"name":"CMA-UBI, Centre of Mathematics and Applications, University of Beira Interior, Rua Marqu\u00eas d\u2019\u00c1vila e Bolama, 6201-001 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5225-6222","authenticated-orcid":false,"given":"Cristina","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Health Sciences Faculty, University of Beira Interior (FCS-UBI), 6200-506 Covilh\u00e3, Portugal"},{"name":"Health Sciences Research Centre, University of Beira Interior (CICS-UBI), 6200-506 Covilh\u00e3, Portugal"},{"name":"UFBI\u2014Pharmacovigilance Unit of Beira Interior, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3333-5977","authenticated-orcid":false,"given":"Ana Paula","family":"Duarte","sequence":"additional","affiliation":[{"name":"Health Sciences Faculty, University of Beira Interior (FCS-UBI), 6200-506 Covilh\u00e3, Portugal"},{"name":"Health Sciences Research Centre, University of Beira Interior (CICS-UBI), 6200-506 Covilh\u00e3, Portugal"},{"name":"UFBI\u2014Pharmacovigilance Unit of Beira Interior, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2112-2835","authenticated-orcid":false,"given":"Manuel","family":"Morgado","sequence":"additional","affiliation":[{"name":"Health Sciences Faculty, University of Beira Interior (FCS-UBI), 6200-506 Covilh\u00e3, Portugal"},{"name":"Health Sciences Research Centre, University of Beira Interior (CICS-UBI), 6200-506 Covilh\u00e3, Portugal"},{"name":"Pharmaceutical Services, University Hospital Center of Cova da Beira, 6200-251 Covilh\u00e3, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s10549-017-4518-8","article-title":"Ribociclib plus letrozole versus letrozole alone in patients with de novo HR+, HER2\u2212 advanced breast cancer in the randomized MONALEESA-2 trial","volume":"168","author":"Petrakova","year":"2018","journal-title":"Breast Cancer Res. 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