The Pharmacological Profile of Cyclin-dependent Kinase (CDK) 4/6 Inhibitors: Clinical Management of Toxicity and Drug Interactions Related to CDK 4/6 Inhibitor-based Treatment in Advanced/Metastatic Breast Cancer

[1]D. Hanahan and R. A. Weinberg, “Hallmarks of cancer: The next generation,” Cell, vol. 144, no. 5. Elsevier Inc., pp. 646–674, 2011.HanahanD.WeinbergR. A.“Hallmarks of cancer: The next generation,”Cell1445Elsevier Inc.,646674201110.1016/j.cell.2011.02.013Search in Google Scholar

[2]G. H. Williams and K. Stoeber, “The cell cycle and cancer,” no. October 2011, pp. 352–364, 2012.WilliamsG. H.StoeberK.“The cell cycle and cancer,”no.October2011352364201210.1002/path.3022Search in Google Scholar

[3]B. Cancer, “Clinical Management of Potential Toxicities and Drug Interactions Related to Cyclin-Dependent Kinase 4 / 6 Inhibitors in Breast Cancer : Practical Considerations and Recommendations,” pp. 1–10, 2017.CancerB.“Clinical Management of Potential Toxicities and Drug Interactions Related to Cyclin-Dependent Kinase 4 / 6 Inhibitors in Breast Cancer : Practical Considerations and Recommendations,”1102017Search in Google Scholar

[4]S. Parylo and A. Vennepureddy, “Role of cyclin-dependent kinase 4 / 6 inhibitors in the current and future eras of cancer treatment,” no. May, 2018.ParyloS.VennepureddyA.“Role of cyclin-dependent kinase 4 / 6 inhibitors in the current and future eras of cancer treatment,”no. May, 2018.10.1177/1078155218770904Search in Google Scholar

[5]P. J. Roberts et al., “Multiple Roles of Cyclin-Dependent Kinase 4 / 6 Inhibitors in Cancer Therapy,” vol. 104, no. 6, 2012.RobertsP. J.“Multiple Roles of Cyclin-Dependent Kinase 4 / 6 Inhibitors in Cancer Therapy,”1046201210.1093/jnci/djs002Search in Google Scholar

[6]M. Malumbres and M. Barbacid, “Cell cycle, CDKs and cancer: a changing paradigm,” vol. 9, no. March, 2009.MalumbresM.BarbacidM.“Cell cycle, CDKs and cancer: a changing paradigm,”9no.March200910.1038/nrc2602Search in Google Scholar

[7]R. A. Weinberg, “The Retinoblastoma Protein and Cell Cycle Control Review,” 1995.WeinbergR. A.“The Retinoblastoma Protein and Cell Cycle Control Review,”199510.1016/0092-8674(95)90385-2Search in Google Scholar

[8]K. E. Knudsen, E. Weber, K. C. Arden, W. K. Cavenee, J. R. Feramisco, and E. S. Knudsen, “The retinoblastoma tumor suppressor inhibits cellular proliferation through two distinct mechanisms : inhibition of cell cycle progression and induction of cell death,” pp. 5239–5245, 1999.KnudsenK. E.WeberE.ArdenK. C.CaveneeW. K.FeramiscoJ. R.KnudsenE. S.“The retinoblastoma tumor suppressor inhibits cellular proliferation through two distinct mechanisms : inhibition of cell cycle progression and induction of cell death,”52395245199910.1038/sj.onc.1202910Search in Google Scholar

[9]S. Thomas and A. Balan, “Retinoblastoma Tumor Suppressor Gene : An Overview,” no. January 2012, 2014.ThomasS.BalanA.“Retinoblastoma Tumor Suppressor Gene : An Overview,”no. January 2012201410.5005/jp-journals-10011-1255Search in Google Scholar

[10]L. N. Kent and G. Leone, “The broken cycle : E2F dysfunction in cancer,” Nat. Rev. Cancer, vol. 19, no. June, 2019.KentL. N.LeoneG.“The broken cycle : E2F dysfunction in cancer,”Nat. Rev. Cancer19no.June201910.1038/s41568-019-0143-731053804Search in Google Scholar

[11]T. W. Miller, “Clinical potential of novel therapeutic targets in breast cancer : CDK4 / 6, Src, JAK / STAT, PARP, HDAC, and PI3K / AKT / mTOR pathways,” pp. 203–215, 2014.MillerT. W.“Clinical potential of novel therapeutic targets in breast cancer : CDK4 / 6, Src, JAK / STAT, PARP, HDAC, and PI3K / AKT / mTOR pathways,”203215201410.2147/PGPM.S52762415739725206307Search in Google Scholar

[12]S. Pernas, S. M. Tolaney, E. P. Winer, and S. Goel, “CDK4/6 inhibition in breast cancer: current practice and future directions,” Ther. Adv. Med. Oncol., vol. 10, pp. 1–15, 2018.PernasS.TolaneyS. M.WinerE. P.GoelS.“CDK4/6 inhibition in breast cancer: current practice and future directions,”Ther. Adv. Med. Oncol.10115201810.1177/1758835918786451605081130038670Search in Google Scholar

[13]S. L. Sammons, D. L. Topping, and K. L. Blackwell, “HR+, HER2–Advanced Breast Cancer and CDK4/6 Inhibitors: Mode of Action, Clinical Activity, and Safety Profiles,” pp. 637–649, 2017.SammonsS. L.ToppingD. L.BlackwellK. L.“HR+, HER2–Advanced Breast Cancer and CDK4/6 Inhibitors: Mode of Action, Clinical Activity, and Safety Profiles,”637649201710.2174/1568009617666170330120452Search in Google Scholar

[14]M. Thill and M. Schmidt, “Management of adverse events during cyclin-dependent kinase 4/6 (CDK4/6) inhibitor-based treatment in breast cancer,” Therapeutic Advances in Medical Oncology, vol. 10. SAGE Publications Inc., 01-Jan-2018.ThillM.SchmidtM.“Management of adverse events during cyclin-dependent kinase 4/6 (CDK4/6) inhibitor-based treatment in breast cancer,”Therapeutic Advances in Medical Oncology10SAGE Publications Inc.01Jan201810.1177/1758835918793326Search in Google Scholar

[15]C. K. Osborne and R. Schiff, “Mechanisms of Endocrine Resistance in Breast Cancer,” Annu. Rev. Med., vol. 62, no. 1, pp. 233–247, Jan. 2010.OsborneC. K.SchiffR.“Mechanisms of Endocrine Resistance in Breast Cancer,”Annu. Rev. Med.621233247Jan201010.1146/annurev-med-070909-182917Search in Google Scholar

[16]D. L. Burkhart and J. Sage, “Cellular mechanisms of tumour suppression by the retinoblastoma gene,” Nature Reviews Cancer, vol. 8, no. 9. pp. 671–682, Sep-2008.BurkhartD. L.SageJ.“Cellular mechanisms of tumour suppression by the retinoblastoma gene,”Nature Reviews Cancer89671682Sep200810.1038/nrc2399Search in Google Scholar

[17]E. S. Knudsen and J. Y. J. Wang, “Targeting the RB-pathway in cancer therapy,” Clin. Cancer Res., vol. 16, no. 4, pp. 1094–1099, Feb. 2010.KnudsenE. S.WangJ. Y. J.“Targeting the RB-pathway in cancer therapy,”Clin. Cancer Res.16410941099Feb201010.1158/1078-0432.CCR-09-0787Search in Google Scholar

[18]A. Johnson and J. M. Skotheim, “NIH Public Access,” vol. 25, no. 6, pp. 1–12, 2014.JohnsonA.SkotheimJ. M.“NIH Public Access,”2561122014Search in Google Scholar

[19]No Title. .No Title. .Search in Google Scholar

[20]Y. J. Choi and L. Anders, “Signaling through cyclin D-dependent kinases,” Oncogene, vol. 33, no. 15. Nature Publishing Group, pp. 1890–1903, 10-Apr-2014.ChoiY. J.AndersL.“Signaling through cyclin D-dependent kinases,”Oncogene3315Nature Publishing Group,1890190310Apr201410.1038/onc.2013.137Search in Google Scholar

[21]E. A. Musgrove, C. E. Caldon, J. Barraclough, A. Stone, and R. L. Sutherland, “Cyclin D as a therapeutic target in cancer,” Nat. Publ. Gr., vol. 11, no. 8, pp. 558–572, 2011.MusgroveE. A.CaldonC. E.BarracloughJ.StoneA.SutherlandR. L.“Cyclin D as a therapeutic target in cancer,”Nat. Publ. Gr.118558572201110.1038/nrc3090Search in Google Scholar

[22]J. Lukas, J. Bartkova, and J. Bartek, “Convergence of Mitogenic Signalling Cascades from Diverse Classes of Receptors at the Cyclin D – Cyclin-Dependent Kinase – pRb-Controlled G 1 Checkpoint,” vol. 16, no. 12, pp. 6917–6925, 1996.LukasJ.BartkovaJ.BartekJ.“Convergence of Mitogenic Signalling Cascades from Diverse Classes of Receptors at the Cyclin D – Cyclin-Dependent Kinase – pRb-Controlled G 1 Checkpoint,”161269176925199610.1128/MCB.16.12.6917Search in Google Scholar

[23]E. S. Knudsen and E. Zacksenhaus, “The vulnerability of RB loss in breast cancer : Targeting a void in cell cycle control,” vol. 9, no. 57, pp. 30940–30941, 2018.KnudsenE. S.ZacksenhausE.“The vulnerability of RB loss in breast cancer : Targeting a void in cell cycle control,”9573094030941201810.18632/oncotarget.25797Search in Google Scholar

[24]C. A. Lange and D. Yee, “NIH Public Access,” vol. 18, no. 4, pp. 1–8, 2014.LangeC. A.YeeD.“NIH Public Access,”184182014Search in Google Scholar

[25]D. W. Fry et al., “Specific inhibition of cyclin-dependent kinase 4 / 6 by PD 0332991 and associated antitumor activity in human tumor xenografts,” vol. 3, no. November, pp. 1427–1438, 2004.FryD. W.“Specific inhibition of cyclin-dependent kinase 4 / 6 by PD 0332991 and associated antitumor activity in human tumor xenografts,”3no.November14271438200410.1158/1535-7163.1427.3.11Search in Google Scholar

[26]F. Petrelli et al., “Comparative efficacy of palbociclib, ribociclib and abemaciclib for ER+ metastatic breast cancer: an adjusted indirect analysis of randomized controlled trials,” Breast Cancer Research and Treatment, Springer New York LLC, 30-Apr-2019.PetrelliF.“Comparative efficacy of palbociclib, ribociclib and abemaciclib for ER+ metastatic breast cancer: an adjusted indirect analysis of randomized controlled trials,”Breast Cancer Research and TreatmentSpringer New York LLC30Apr201910.1007/s10549-019-05133-ySearch in Google Scholar

[27]G. K. Schwartz et al., “Phase I study of PD 0332991, a cyclin-dependent kinase inhibitor, administered in 3-week cycles (Schedule 2 / 1),” pp. 1862–1868, 2011.SchwartzG. K.“Phase I study of PD 0332991, a cyclin-dependent kinase inhibitor, administered in 3-week cycles (Schedule 2 / 1),”18621868201110.1038/bjc.2011.177Search in Google Scholar

[28]A. Demichele et al., “Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer,” pp. 1–11, 2018.DemicheleA.“Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer,”1112018Search in Google Scholar

[29]R. S. Finn et al., “The cyclin-dependent kinase 4 / 6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1 / TRIO-18): a randomised phase 2 stud,” Lancet Oncol., pp. 1–11.FinnR. S.“The cyclin-dependent kinase 4 / 6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1 / TRIO-18): a randomised phase 2 stud,”Lancet Oncol.11110.1016/S1470-2045(14)71159-3Search in Google Scholar

[30]H. S. R. R. S. F. V Diéras, J. E. O. Lipatov, A. A. J. N. Harbeck, and A. C. S. Iyer, “Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive / human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up,” Breast Cancer Res. Treat., vol. 174, no. 3, pp. 719–729, 2019.R.H. S.F.R. S.DiérasVE.J.LipatovO.J.A. A.HarbeckN.C.A.IyerS.“Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive / human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up,”Breast Cancer Res. Treat1743719729201910.1007/s10549-018-05125-4643894830632023Search in Google Scholar

[31]N. C. Turner et al., “Palbociclib in Hormone-Receptor–Positive Advanced Breast Cancer,” N. Engl. J. Med., vol. 373, no. 3, pp. 209–219, Jul. 2015.TurnerN. C.“Palbociclib in Hormone-Receptor–Positive Advanced Breast Cancer,”N. Engl. J. Med.3733209219Jul.201510.1056/NEJMoa150527026030518Search in Google Scholar

[32]H. Iwata et al., “PALOMA-3: Phase III Trial of Fulvestrant With or Without Palbociclib in Premenopausal and Postmenopausal Women With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer That Progressed on Prior Endocrine Therapy—Safety and Efficacy in Asian Patients,” J. Glob. Oncol., vol. 3, no. 4, pp. 289–303, Aug. 2017.IwataH.“PALOMA-3: Phase III Trial of Fulvestrant With or Without Palbociclib in Premenopausal and Postmenopausal Women With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer That Progressed on Prior Endocrine Therapy—Safety and Efficacy in Asian Patients,”J. Glob. Oncol.34289303Aug.201710.1200/JGO.2016.008318556046528831437Search in Google Scholar

[33]G. N. Hortobagyi et al., “Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer,” N. Engl. J. Med., vol. 375, no. 18, pp. 1738–1748, 2016.HortobagyiG. N.“Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer,”N. Engl. J. Med.3751817381748201610.1056/NEJMoa160970927717303Search in Google Scholar

[34]G. N. Hortobagyi et al., “Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer Original article,” no. April, pp. 1541–1547, 2018.HortobagyiG. N.“Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer Original article,”no.April15411547201810.1093/annonc/mdy155Search in Google Scholar

[35]G. Curigliano et al., “Ribociclib plus letrozole in early breast cancer: A presurgical, window-of-opportunity study,” Breast, vol. 28, pp. 191–198, Aug. 2016.CuriglianoG.“Ribociclib plus letrozole in early breast cancer: A presurgical, window-of-opportunity study,”Breast28191198Aug.201610.1016/j.breast.2016.06.00827336726Search in Google Scholar

[36]D. J. Slamon et al., “JOURNAL OF CLINICAL ONCOLOGY Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: MONALEESA-3,” J Clin Oncol, vol. 36, pp. 2465–2472, 2018.SlamonD. J.“JOURNAL OF CLINICAL ONCOLOGY Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: MONALEESA-3,”J Clin Oncol3624652472201810.1200/JCO.2018.78.990929860922Search in Google Scholar

[37]O. Article, “Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer,” pp. 1–10, 2019.O. Article,“Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer,”1102019Search in Google Scholar

[38]E. C. Ehman et al., “HHS Public Access,” vol. 46, no. 5, pp. 1247–1262, 2017.EhmanE. C.“HHS Public Access,”46512471262201710.1002/jmri.25711Search in Google Scholar

[39]G. W. Sledge et al., “MONARCH 2: Abemaciclib in combination with fulvestrant in women with HR+/HER2-advanced breast cancer who had progressed while receiving endocrine therapy,” J. Clin. Oncol., vol. 35, no. 25, pp. 2875–2884, 2017.SledgeG. W.“MONARCH 2: Abemaciclib in combination with fulvestrant in women with HR+/HER2-advanced breast cancer who had progressed while receiving endocrine therapy,”J. Clin. Oncol.352528752884201710.1200/JCO.2017.73.758528580882Search in Google Scholar

[40]M. P. Goetz et al., “MONARCH 3 : Abemaciclib As Initial Therapy for Advanced Breast Cancer,” vol. 35, no. 32, 2019.GoetzM. P.“MONARCH 3 : Abemaciclib As Initial Therapy for Advanced Breast Cancer,”3532201910.1200/JCO.2017.75.615528968163Search in Google Scholar

[41]S. Johnston et al., “MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer,” npj Breast Cancer, vol. 5, no. 1, Dec. 2019.JohnstonS.“MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer,”npj Breast Cancer51Dec.201910.1038/s41523-018-0097-z633688030675515Search in Google Scholar

[42]N. Masuda, K. Inoue, R. Nakamura, Y. Rai, H. Mukai, and S. Ohno, “Palbociclib in combination with fulvestrant in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer : PALOMA-3 subgroup analysis of Japanese patients,” Int. J. Clin. Oncol., vol. 0, no. 0, p. 0, 2018.MasudaN.InoueK.NakamuraR.RaiY.MukaiH.OhnoS.“Palbociclib in combination with fulvestrant in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer : PALOMA-3 subgroup analysis of Japanese patients,”Int. J. Clin. Oncol.000201810.1007/s10147-018-1359-3639917030392115Search in Google Scholar

[43]K. Gelmon et al., “new england journal,” pp. 1925–1936, 2016.GelmonK.“new england journal,”19251936201610.1056/NEJMoa160730327959613Search in Google Scholar

[44]J. K. Kish et al., “Real-world evidence analysis of palbociclib prescribing patterns for patients with advanced / metastatic breast cancer treated in community oncology practice in the USA one year post approval,” pp. 1–8, 2018.KishJ. K.“Real-world evidence analysis of palbociclib prescribing patterns for patients with advanced / metastatic breast cancer treated in community oncology practice in the USA one year post approval,”18201810.1186/s13058-018-0958-2593281929720233Search in Google Scholar

[45]US Food and Drug Administration, “Ibrance. Prescribing information.,” Https://Www.Accessdata.Fda.Gov/Drugsatfda_Docs/Label/2017/207103S004Lbl.Pdf 2017.US Food and Drug Administration“Ibrance. Prescribing information.,”Https://Www.Accessdata.Fda.Gov/Drugsatfda_Docs/Label/2017/207103S004Lbl.Pdf2017Search in Google Scholar

[46]CHMP, “ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS.”CHMP“ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS.”Search in Google Scholar

[47]Epar, “ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS.”Epar“ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS.”Search in Google Scholar

[48]C. Van Noord, M. Eijgelsheim, and B. H. C. Stricker, “Drug- and non-drug-associated QT interval prolongation,” British Journal of Clinical Pharmacology, vol. 70, no. 1. pp. 16–23, Jul-2010.Van NoordC.EijgelsheimM.StrickerB. H. C.“Drug- and non-drug-associated QT interval prolongation,”British Journal of Clinical Pharmacology7011623Jul201010.1111/j.1365-2125.2010.03660.x290980320642543Search in Google Scholar

[49]J. C. Chappell et al., “Abemaciclib Inhibits Renal Tubular Secretion Without Changing Glomerular Filtration Rate,” Clinical Pharmacology and Therapeutics, Nature Publishing Group, 2019.ChappellJ. C.“Abemaciclib Inhibits Renal Tubular Secretion Without Changing Glomerular Filtration Rate,”Clinical Pharmacology and TherapeuticsNature Publishing Group201910.1002/cpt.1296646509930449032Search in Google Scholar