{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:20:58Z","timestamp":1790011258375,"version":"4.0.1"},"reference-count":97,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2018,5,4]],"date-time":"2018-05-04T00:00:00Z","timestamp":1525392000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Oncol Pharm Pract"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:p>Cyclin-dependent kinase 4\/6 inhibitors, which act by inhibiting progression from the G1 to S phases of the cell cycle, include palbociclib, ribociclib, abemaciclib, and trilaciclib. Palbociclib and ribociclib are currently food and drug administration-approved for use in combination with aromatase inhibitors in postmenopausal women with metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Palbociclib is also food and drug administration-approved for use in combination with fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer progressing after endocrine therapy. Abemaciclib is the newest cyclin-dependent kinase 4\/6 inhibitor to gain Food and Drug Administration (FDA) approval, specifically as monotherapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer previously treated with chemotherapy and endocrine therapy. Abemaciclib also shares a similar indication with palbociclib for use in combination with fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer progressing after endocrine therapy. Trilaciclib use remains largely investigational at this time. However, despite FDA-approval for only metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer, all four cyclin-dependent kinase 4\/6 inhibitors have shown promise in hematologic malignancies and non-breast solid tumors. Although further research is needed, cyclin-dependent kinase 4\/6 inhibitors represent intriguing developments in the treatment of various malignancies, including those with such poor prognoses as glioblastoma multiforme, mantle cell lymphoma, and metastatic melanoma. We discuss the approved indications, current research, and areas of future exploration for palbociclib, ribociclib, abemaciclib, and trilaciclib.<\/jats:p>","DOI":"10.1177\/1078155218770904","type":"journal-article","created":{"date-parts":[[2018,5,4]],"date-time":"2018-05-04T09:43:30Z","timestamp":1525427010000},"page":"110-129","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":36,"title":["Role of cyclin-dependent kinase 4\/6 inhibitors in the current and future eras of cancer treatment"],"prefix":"10.1177","volume":"25","author":[{"given":"S","family":"Parylo","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Staten Island University Hospital, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Vennepureddy","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Staten Island University Hospital, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Dhar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Staten Island University Hospital, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Patibandla","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Staten Island University Hospital, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Sokoloff","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Staten Island University Hospital, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2018,5,4]]},"reference":[{"key":"bibr1-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2602"},{"key":"bibr2-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1186\/bcr3064"},{"key":"bibr3-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)71159-3"},{"key":"bibr4-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1607303"},{"key":"bibr5-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1177\/1758834016677961"},{"key":"bibr6-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00613-0"},{"key":"bibr7-1078155218770904","unstructured":"FDA approves abemaciclib for HR-positive, HER2-negative breast cancer\n                      , www.fda.gov\/drugs\/informationondrugs\/approveddrugs\/ucm578081.htm (2017, accessed 5 October 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N.I.o.\n                      palbociclib, mantle cell lymphoma\n                      , https:\/\/clinicaltrials.gov\/ct2\/results?term=palbociclib+mantle+cell+lymphoma&pg=1 (2017, 25 September 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Ribociclib improved progression-free survival for pre- and perimenopausal women with hormone receptor positive advanced breast cancer. In:\n                      San Antonio Breast Cancer Symposium\n                      , 2017. pp.1\u20132."},{"key":"bibr47-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-2898"},{"key":"bibr48-1078155218770904","first-page":"572","volume":"7","author":"Sandru A","year":"2014","journal-title":"J Med Life"},{"key":"bibr49-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2014.32.15_suppl.9009"},{"key":"bibr50-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-3157"},{"key":"bibr51-1078155218770904","first-page":"374","volume":"25","author":"Taylor M","year":"2014","journal-title":"Oncology"},{"key":"bibr52-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2014.32.15_suppl.535"},{"key":"bibr53-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.SABCS16-P4-22-18"},{"key":"bibr54-1078155218770904","unstructured":"Tolaney SM, et\u00a0al. Ribociclib + fulvestrant in postmenopausal women with HR+, HER2\u2013 advanced breast cancer (ABC). In:\n                      San Antonio Breast Cancer Symposium\n                      , 6\u201310 December 2016, Springer Healthcare Limited: San Antonio, Texas. pp.1027\u20131028."},{"key":"bibr55-1078155218770904","unstructured":"Bardia A, et\u00a0al. Triplet therapy with ribociclib, everolimus, and exemestane in women with HR+\/HER2\u2013 advanced breast cancer. In:\n                      San Antonio Breast Cancer Symposium,\n                      8\u201312 December 2015, Springer Healthcare Limited: San Antonio, Texas. p.1436."},{"key":"bibr56-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-0754"},{"key":"bibr57-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.73.7585"},{"key":"bibr58-1078155218770904","doi-asserted-by":"crossref","unstructured":"Goetz MP, et\u00a0al.\n                      MONARCH 3: A randomized phase III study of anastrozole or letrozole plus abemaciclib, a CDK4\/6 inhibitor, or placebo in first-line treatment of women with HR+, HER2-locoregionally recurrent or metastatic breast cancer (MBC)\n                      . Journal of Clinical Oncology, May 29-June 2, 2015; 33(15_suppl): pp.TPS624-TPS624.","DOI":"10.1200\/jco.2015.33.15_suppl.tps624"},{"key":"bibr59-1078155218770904","doi-asserted-by":"crossref","unstructured":"Abemaciclib shows promise for early breast cancer.\n                      Cancer Discov\n                      2017; 7: 119\u2013120.","DOI":"10.1158\/2159-8290.CD-NB2016-160"},{"key":"bibr60-1078155218770904","doi-asserted-by":"crossref","unstructured":"Hurvitz S, et\u00a0al. Interim results from neoMONARCH: a neoadjuvant phase II study of abemaciclib in postmenopausal women with HR+\/HER2-breast cancer (BC). In:\n                      Annals of oncology\n                      , 16\u201320 April 2016. Oxford OX2 6DP, England: Oxford Univ Press Great Clarendon St.","DOI":"10.1093\/annonc\/mdw435.02"},{"key":"bibr61-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1016\/j.cllc.2015.08.003"},{"key":"bibr62-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2017.1376741"},{"key":"bibr63-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-16-0095"},{"key":"bibr64-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-016-3085-8"},{"key":"bibr65-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw435.08"},{"key":"bibr66-1078155218770904","unstructured":"Highlights of prescribing information, www.accessdata.fda.gov\/drugsatfda_docs\/label\/2017\/208716s000lbl.pdf (2017, accessed 19 March 2018)."},{"key":"bibr67-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.75.6155"},{"key":"bibr68-1078155218770904","unstructured":"NIH, U.N.L.o.M. abemaciclib, https:\/\/clinicaltrials.gov\/ct2\/results?cond=&term=abemaciclib&cntry1=&state1=&Search=Search#tableTop (2017, 26 September 2017)."},{"key":"bibr69-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aal3986"},{"key":"bibr70-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1172\/JCI41402"},{"key":"bibr71-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djs002"},{"key":"bibr72-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-15-0775"},{"key":"bibr73-1078155218770904","doi-asserted-by":"publisher","DOI":"10.2174\/1568009617666170330120452"},{"key":"bibr74-1078155218770904","doi-asserted-by":"publisher","DOI":"10.7812\/TPP\/14-241"},{"key":"bibr75-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.38.1095"},{"key":"bibr76-1078155218770904","unstructured":"Mitchell M.\n                      Increasing focus on value related to cancer drugs: a payer perspective\n                      , 2017."},{"key":"bibr77-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx201"},{"key":"bibr78-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2016.03.1589"},{"key":"bibr79-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-016-3822-z"},{"key":"bibr80-1078155218770904","first-page":"635","volume":"163","author":"Matter-Walstra K","year":"2017","journal-title":"revised results for the Swiss health care setting. Breast Cancer Res Treat"},{"key":"bibr81-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2017.1351947"},{"key":"bibr82-1078155218770904","unstructured":"Ibrance dosing and administration guide, www.pfizerpro.com\/sites\/default\/files\/ibrance_nurse_dosing_guide.pdf (2015, accessed 18 January 2018)."},{"key":"bibr83-1078155218770904","doi-asserted-by":"crossref","first-page":"A422","DOI":"10.1016\/j.jval.2017.08.145","volume":"20","author":"Mistry R","year":"2017","journal-title":"Value in Health"},{"key":"bibr84-1078155218770904","doi-asserted-by":"crossref","first-page":"A433","DOI":"10.1016\/j.jval.2017.08.202","volume":"20","author":"Hettle R","year":"2017","journal-title":"Value in Health"},{"key":"bibr85-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12228"},{"key":"bibr86-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-12-0562"},{"key":"bibr87-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-0244"},{"key":"bibr88-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-0829"},{"key":"bibr89-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-0589"},{"key":"bibr90-1078155218770904","first-page":"2997","volume":"33","author":"Logan JE","year":"2013","journal-title":"Anticancer Res"},{"key":"bibr91-1078155218770904","unstructured":"Health, N.I.o.\n                      Study of palbociclib in MLL-rearranged acute leukemias\n                      , https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02310243?term=palbociclib&rank=3 (2017, accessed 25 September 2017)."},{"key":"bibr92-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.12072"},{"key":"bibr93-1078155218770904","doi-asserted-by":"crossref","unstructured":"Lenihan C, Bouchekioua-Bouzaghou K, Abdulghani R, et\u00a0al. CDK4\/6 inhibitor resistant ER-positive cells remain dependent on estrogen signalling and retain sensitivity to endocrine therapy. In:\n                      San Antonio breast cancer symposium\n                      , 2016, Philadelphia, PA: AACR;\n                      Cancer Res\n                      2017;77:Abstract nr P3-03-12.: San Antonio, Texas.","DOI":"10.1158\/1538-7445.SABCS16-P3-03-12"},{"key":"bibr94-1078155218770904","doi-asserted-by":"crossref","unstructured":"Hurvitz S, et\u00a0al. Ribociclib in combination with everolimus and exemestane in men and postmenopausal women with HR+\/HER2\u2212 advanced breast cancer following progression on a CDK4\/6 inhibitor: safety, tolerability, and pharmacokinetic results from Phase 1 of TRINITI-1 study [abstract]. In:\n                      American Association for Cancer Research\n                      . 1\u20135 April 2017, American Association for Cancer Research: Washington, DC. p.CT110.","DOI":"10.1158\/1538-7445.AM2017-CT110"},{"key":"bibr95-1078155218770904","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00561"},{"key":"bibr96-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-017-1309-2"},{"key":"bibr97-1078155218770904","doi-asserted-by":"publisher","DOI":"10.1007\/s11864-014-0305-5"}],"container-title":["Journal of Oncology Pharmacy Practice"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1078155218770904","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1078155218770904","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1078155218770904","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T02:18:25Z","timestamp":1777688305000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1078155218770904"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,4]]},"references-count":97,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,1]]}},"alternative-id":["10.1177\/1078155218770904"],"URL":"https:\/\/doi.org\/10.1177\/1078155218770904","relation":{},"ISSN":["1078-1552","1477-092X"],"issn-type":[{"value":"1078-1552","type":"print"},{"value":"1477-092X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,4]]}}}