{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T22:46:16Z","timestamp":1793400376194,"version":"4.5.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T00:00:00Z","timestamp":1698278400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>The personalization of therapies in breast cancer has favoured the introduction of new molecular-targeted therapies into clinical practice. Among them, cyclin-dependent kinases 4 and 6 (CDK4\/6) inhibitors have acquired increasing importance, with the approval in recent years of palbociclib, ribociclib, and abemaciclib in combination with endocrine therapy. Currently, no guidelines are available to monitor and manage potential long-term toxicities associated with the use of these drugs. A multidisciplinary panel of European oncologists, was supported by a pharmacologist, a hematologist, a hepatologist and a pulmonologist to discuss the management of long-term toxicities, based on the literature review and their clinical experience. The panel provided detailed roadmaps to manage long-term toxicities associated with the use of CDK4\/6 inhibitors in clinical practice. Knowing the frequency and characteristics of the toxicity profile associated with each CDK4\/6 inhibitor is important in the decision-making process to match the right drug to the right patient.<\/jats:p>","DOI":"10.3389\/fonc.2023.1247270","type":"journal-article","created":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T23:30:09Z","timestamp":1698363009000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Late onset toxicities associated with the use of CDK 4\/6 inhibitors in hormone receptor positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) metastatic breast cancer patients: a multidisciplinary, pan-EU position paper regarding their optimal management. The GIOCONDA project"],"prefix":"10.3389","volume":"13","author":[{"given":"Marina Elena","family":"Cazzaniga","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Ciaccio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romano","family":"Danesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francois P.","family":"Duhoux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corrado","family":"Girmenia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalhil","family":"Zaman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Lindman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Luppi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Mavroudis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Paris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayodele","family":"Olubukola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Samreen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Schem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Singer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Snegovoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2022.103866","article-title":"Systemic treatment for hormone receptor-positive\/HER2-negative advanced\/metastatic breast cancer: A review of European real-world evidence studies","volume":"180","author":"Vieira","year":"2022","journal-title":"Crit Rev Oncol Hematol"},{"key":"B2","volume-title":"Ibrance (palbociclib): EPAR - summary for the public","year":"2020"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2021.09.019","article-title":"ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer","volume":"32","author":"Gennari","year":"2021","journal-title":"Ann Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-3032","article-title":"Updated Overall Survival of Ribociclib plus Endocrine Therapy versus Endocrine Therapy Alone in Pre- and Perimenopausal Patients with HR+\/HER2- Advanced Breast Cancer in MONALEESA-7: A Phase III Randomized Clinical Trial","volume":"28","author":"Lu","year":"2022","journal-title":"Clin Cancer Res"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2021.05.353","article-title":"Ribociclib plus fulvestrant for postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in the phase III randomized MONALEESA-3 trial: updated overall survival","volume":"32","author":"Slamon","year":"2021","journal-title":"Ann Oncol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1038\/s41523-022-00479-x","article-title":"Real-world study of overall survival with palbociclib plus aromatase inhibitor in HR+\/HER2- metastatic breast cancer","volume":"8","author":"Rugo","year":"2022","journal-title":"NPJ Breast Cancer"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1080\/03007995.2021.1923468","article-title":"Real-world treatment patterns and outcomes of abemaciclib for the treatment of HR+, HER2- metastatic breast cancer","volume":"37","author":"Cuyun Carter","year":"2021","journal-title":"Curr Med Res Opin"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1080\/14737140.2019.1615889","article-title":"Recent advances with cyclin-dependent kinase inhibitors: therapeutic agents for breast cancer and their role in immuno-oncology","volume":"19","author":"Di Sante","year":"2019","journal-title":"Expert Rev Anticancer Ther"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1080\/14737140.2021.1852934","article-title":"CDK4\/6 inhibitors in breast cancer: differences in toxicity profiles and impact on agent choice","volume":"21","author":"Onesti","year":"2021","journal-title":"A systematic Rev meta-analysis. Expert Rev Anticancer Ther"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2020.102086","article-title":"Comparison of treatment-related adverse events of different Cyclin-dependent kinase 4\/6 inhibitors in metastatic breast cancer: A network meta-analysis","volume":"90","author":"Desnoyers","year":"2020","journal-title":"Cancer Treat Rev"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-1421","article-title":"Mechanistic investigation of bone marrow suppression associated with palbociclib and its differentiation from cytotoxic chemotherapies","volume":"22","author":"Hu","year":"2016","journal-title":"Clin Cancer Res"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-022-07320-y","article-title":"Infectious complications of cyclin-dependent kinases 4 and 6 inhibitors in patients with hormone-receptor-positive metastatic breast cancer: a systematic review and meta-analysis","volume":"30","author":"Bas","year":"2022","journal-title":"Support Care Cancer"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.SABCS20-PS13-25","article-title":"Abstract PS13-25: Management of abemaciclib associated diarrhea in patients with hormone receptor-positive\/human epidermal growth factor receptor 2-negative advanced breast cancer: Analysis of the MONARCH plus study. Cancer Research","volume":"81","author":"Jiang","year":"2021","journal-title":"Cancer research"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/onco.13531","article-title":"Management of abemaciclib-associated adverse events in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: safety analysis of MONARCH 2 and MONARCH 3","volume":"26","author":"Rugo","year":"2021","journal-title":"Oncologist"},{"key":"B15","doi-asserted-by":"crossref","DOI":"10.1200\/JCO.2021.39.15_suppl.1072","article-title":"Relative risk of hepatotoxicity associated with cyclin-dependent kinase inhibitors (CDK4\/6i): A systematic review and meta-analysis of phase 3 randomized controlled trials","volume":"39","author":"Jahan","year":"2021","journal-title":"J Clin Oncol"},{"key":"B16","doi-asserted-by":"crossref","first-page":"S36","DOI":"10.1016\/S1590-8658(22)00444-3","article-title":"T.08.1 Characteristics and predictors of liver toxicity in advanced breast cancer patients treated with cyclindependent kinase inhibitors: an observational study","volume":"54","author":"Ciaccio","year":"2022","journal-title":"Digestive Liver Dis"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.01235","article-title":"Strategies for early prediction and timely recognition of drug-induced liver injury: the case of cyclin-dependent kinase 4\/6 inhibitors","volume":"10","author":"Raschi","year":"2019","journal-title":"Front Pharmacol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1080\/0284186X.2020.1853228","article-title":"Hepatotoxicity associated with ribociclib among breast cancer patients","volume":"60","author":"Finnsdottir","year":"2021","journal-title":"Acta Oncol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.breast.2020.10.007","article-title":"Safety and efficacy of cyclin-dependent kinase inhibitor rechallenge following ribociclib-induced limiting hypertransaminasemia","volume":"54","author":"Fuentes-Antras","year":"2020","journal-title":"Breast"},{"key":"B20","doi-asserted-by":"crossref","DOI":"10.1016\/S0168-8278(22)01153-9","article-title":"FRI024 - Liver toxicity associated to novel cyclin-dependent kinase inhibitor ribociclib in a cohort of advanced breast cancer patients","volume":"77","author":"Scaravaglio","year":"2022","journal-title":"J Hepatol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.breast.2022.02.011","article-title":"Interstitial lung disease in patients treated with Cyclin-Dependent Kinase 4\/6 inhibitors: A systematic review and meta-analysis of randomized controlled trials","volume":"62","author":"Zhang","year":"2022","journal-title":"Breast"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-020-06001-w","article-title":"Cyclin-dependent kinase 4\/6 inhibitors and interstitial lung disease in the FDA adverse event reporting system: a pharmacovigilance assessment","volume":"186","author":"Raschi","year":"2021","journal-title":"Breast Cancer Res Treat"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1296","article-title":"Abemaciclib inhibits renal tubular secretion without changing glomerular filtration rate","volume":"105","author":"Chappell","year":"2019","journal-title":"Clin Pharmacol Ther"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.SABCS16-P6-15-01","article-title":"Analysis of renal function in MONARCH 1: A phase 2 study of abemaciclib, a CDK4 & 6 inhibitor, as monotherapy, in patients with HR+\/HER2- breast cancer, after chemotherapy for metastatic breast cancer (MBC)","author":"Tolaney S","year":"2016","journal-title":"San Antonio Breast Cancer Symposium"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2019.101913","article-title":"Corrigendum to \u201cDrug-drug interactions in breast cancer patients treated with CDK4\/6 inhibitors\u201d [Cancer Treatm. Rev. 74 (2019) 21-28]","volume":"81","author":"Fogli","year":"2019","journal-title":"Cancer Treat Rev"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/pds.1211","article-title":"Hy\u2019s law: predicting serious hepatotoxicity","volume":"15","author":"Temple","year":"2006","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"B27","volume-title":"Summary of product characteristics - Verzenio","author":"Verzenio","year":""},{"key":"B28","volume-title":"Summary of product characteristics - Kisqali","author":"Kisqali","year":""},{"key":"B29","volume-title":"Summary of product characteristics - Ibrance","author":"Ibrance","year":""},{"key":"B30","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/S1470-2045(22)00694-5","article-title":"Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial","volume":"24","author":"Johnston","year":"2023","journal-title":"Lancet Oncol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"LBA500","DOI":"10.1200\/JCO.2023.41.17_suppl.LBA500","article-title":"Ribociclib and endocrine therapy as adjuvant treatment in patients with HR+\/HER2\u2013 early breast cancer: Primary results from the phase III NATALEE trial","author":"Slamon","year":"2023","journal-title":"J Clin Oncol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2023.1247270\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T23:30:17Z","timestamp":1698363017000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2023.1247270\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,26]]},"references-count":31,"alternative-id":["10.3389\/fonc.2023.1247270"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2023.1247270","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,26]]},"article-number":"1247270"}}