PRACTICAL ASPECTS OF ADMINISTERING CYCLIN-DEPENDENT KINASES INHIBITORS: EFFICACY AND TOLERABILITY
https://doi.org/10.17650/1994-4098-2018-14-1-52-60
Abstract
Although metastatic breast cancer remains an incurable disease, significant achievements have been made in this area over the recent years, allowing to convert breast cancer into a chronically controlled disease characterized by a torpid course. Patients with hormone-sensitive HER2-negative cancer are more likely to achieve this relatively favorable clinical outcome. It became possible with the development and implementation of highly effective combination treatment regimens that include recently developed inhibitors of cyclin-dependent kinases (CDK) 4 and 6. This article presents an overview of randomized clinical trials assessing the efficacy and safety of CDK4/6 inhibitors. It is shown that neutropenia is class-specific undesirable effect and characterizes all 3 drugs (palbociclib, ribociclib, abemaciclib); ribociclib therapy, in addition, is associated with hepatoand cardiotoxicity (prolongation of QTc interval); abemaciclib, in addition to neutropenia, is characterized by diarrhea and thromboembolic events.
About the Author
E. V. Artamonova
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation
23 Kashirskoe Shosse, Moscow 115478
Russian Federation
23 Kashirskoe Shosse, Moscow 115478
References
1. Rugo H.S., Rumble R.B., Macrae E. et al. Endocrine therapy for hormone receptorpositive metastatic breast cancer: American Society of Clinical Oncology Guideline. J Clin Oncol 2016;(25):3069–103. DOI:10.1200/JCO.2016.67.1487.
2. Wilcken N., Hornbuckle J., Ghersi D. Chemotherapy alone versus endocrine therapy alone for metastatic breast cancer. Cochrane Database Syst Rev 2003;(2):CD002747. PMID: 12804433. DOI: 10.1002/14651858.CD002747.
3. Mauri D., Pavlidis N., Polysos N.P., Ioannidis J.P. Survival with aromatase inhibitors and inactivators versus standard hormonal therapy in advanced breast cancer: meta-analysis. J Natl Cancer Inst 2006;98(18):1285–91. PMID: 16985247. DOI: 10.1093/jnci/djj357.
4. Bonneterre J., Thürlimann B., Robertson J.F. et al. Anastrozole versus tamoxifen as first-line therapy for advanced breast cancer in 668 postmenopausal women: results of the tamoxifen or arimidex randomized group efficacy and tolerability study. J Clin Oncol 2000;18(22):3748–57. PMID: 11078487. DOI: 10.1200/JCO.2000.18.22.3748.
5. Mouridsen H., Gershanovich M., Sun Y. et al. Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group. J Clin Oncol 2001;19(10):2596– 606. PMID: 11352951. DOI: 10.1200/JCO.2001.19.10.2596.
6. Mouridsen H., Gershanovich M., Sun Y. et al. Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group. J Clin Oncol 2003;21(11):2101–9. PMID: 12775735. DOI: 10.1200/JCO.2003.04.194.
7. Robertson J.F.R., Lindemann J.P.O., Llombart-Cussac A. et al. A comparison of fulvestrant 500 mg with anastrozole as first-line treatment for advanced breast cancer: follow-up analysis from the “FIRST” study. Presented at 33rd Annual San Antonio Breast Cancer Symposium, Dec 8–12, 2010, San Antonio, Texas, USA. Abstr. S1–3.
8. Osborne C.K., Pippen J., Jones S.E. et al. Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American Trial. J Clin Oncol 2002;20(16):3386–95. PMID: 12177098. DOI: 10.1200/JCO.2002.10.058.
9. Howell A., Robertson J.F., Quaresma Albano J. et al. Fulvestrant, formerly ICI 182780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. Clin Oncol 2002;20(16):3396–403. PMID: 12177099. DOI: 10.1200/JCO.2002.10.057.
10. Chia S., Gradishar W., Mauriac L. et al. Double-blind, randomized placebo controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive, advanced breast cancer: results from EFECT. J Clin Oncol 2008;26(10):1664– 70. PMID: 18316794. DOI: 10.1200/JCO.2007.13.5822.
11. Steele N., Zekri J., Coleman R. et al. Exemestane in metastatic breast cancer: effective therapy after third-generation non-steroidal aromatase inhibitor failure. Breast 2006;15(3):430–6. PMID: 16236514. DOI: 10.1016/j.breast.2005.08.032.
12. Carlini P., Michelotti A., Ferretti G. et al. Clinical evaluation of the use of exemestane as further hormonal therapy after nonsteroidal aromatase inhibitors in postmenopausal metastatic breast cancer patients. Cancer Invest 2007;25(2):102–5. PMID: 17453821. DOI: 10.1080/07357900701224789.
13. Lonning P.E., Bajetta E., Murray R. et al. Activity of exemestane in metastatic breast cancer after failure of nonsteroidal aromatase inhibitors: a phase II trial. J Clin Oncol 2000;18(11):2234–44. PMID: 10829043. DOI: 10.1200/JCO.2000.18.11.2234.
14. Baselga J., Campone M., Piccart M. et al. Everolimus in postmenopausal hormonereceptorpositive advanced breast cancer. N Engl J Med 2012;(366):520–29.
15. Cardoso F., Costa A., Norton L. et al. ESO-ESMO 2nd international consensus guidelines for advanced breast cancer (ABC2). Ann Oncol 2014;25(10): 1871–88. PMID: 25234545. DOI: 10.1093/annonc/mdu385.
16. Hirama T., Koeffler P.H. Role of the cyclindependent kinase inhibitors in the development of cancer. Blood 1995;86(3):841–54. PMID: 7620180.
17. Fry D.W., Harvey P.J., Keller P.R. et al. Specific Inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther 2004;3(11):1427– 38. PMID: 15542782.
18. Choi Y.J., Anders L. Signaling through cyclin D-dependent kinases. Oncogene 2014;33(15):1890–903. PMID: 23644662. DOI: 10.1038/onc.2013.137.
19. The Nobel Prize in Physiology or Medicine 2001: press release. Available at: https://www.nobelprize.org/nobel_prizes/medicine/laureates/2001/press.html.
20. Finn R.S., Dering J., Conklin D. et al. PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. Breast Cancer Res 2009;11(5):R77. PMID: 19874578. DOI: 10.1186/bcr2419.
21. Lamb R., Lehn S., Rogerson L. et al. Cell cycle regulators cyclin D1 and CDK4/6 have estrogen receptor-dependent divergent functions in breast cancer migration and stem cell-like activity. Cell Cycle 2013;12(15):2384–94. PMID: 23839043. DOI: 10.4161/cc.25403.
22. Finn R.S., Crown J.P., Lang I. 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 study. Lancet Oncol 2015;16(1):25–35. PMID: 25524798. DOI: 10.1016/S1470-2045(14)71159-3.
23. Finn R.S., Crown J.P., Ettl J. et al. Efficacy and safety of palbociclib in combination with letrozole as first-line treatment of ER-positive, HER2-negative, advanced breast cancer: expanded analyses of subgroups from randomized pivotal trial PALOMA-1/TRIO-18. Breast Cancer Res 2016;18(1):67. PMID: 27349747. DOI: 10.1186/s13058-016-0721-5.
24. Finn R.S., Crown J.P., Lang I. et al. Overall survival from randomized phase 2 study of palbociclib in combination with letrozole vs. letrozole alone for first-line treatment of ER+/HER2– advanced breast cancer (PALOMA-1; TRIO-18). ASCO2017. Abstr. 1001.
25. Finn R.S., Martin M., Rugo H.S. et al. PALOMA-2: primary results from a phase III trial of palbociclib (P) with letrozole (L) compared with letrozole alone in postmenopausal women with ER+/HER2– advanced breast cancer (ABC). J Clin Oncol 2016;34(Suppl):507.
26. Turner N.C., Ro J., Andre F. et al. Palbociclib in hormone-receptor-positive advanced breast cancer. N Engl J Med 2015;373(3):209–19. DOI: 10.1056/NEJMoa1505270.
27. Finn R.S., Martin M., Rugo H.S. et al. Palbociclib and letrozole in advanced breast cancer. NEJM 2016;(375):1925–36.
28. Finn R.S., Dieras V., Rugo H.S. et al. Palbociclib (PAL) + letrozole (L) as first-line (1L) therapy (tx) in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC): efficacy and safety across patient (pt) subgroups. J Clin Oncol 2017;35(Suppl):1039.
29. Rugo H.S., Finn R.S., Dieras V. et al. Palbociclib (PAL) + Letrozole (LET) as firstline therapy in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC): efficacy and safety updates with longer follow-up across patient subgroups. Presented at 2017 San Antonio Breast Cancer Symposium, Dec 5–9, 2017, San Antonio, Texas, USA. Abstr. P5-21-03.
30. Cristofanilli M., Turner N.C., Bondarenko I. et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol 2016;17(4):425–39. PMID: 26947331. DOI: 10.1016/S1470-2045(15)00613-0.
31. Cristofanilli M., Bondarenko I., Ro J. et al. PALOMA-3: Phase 3 trial of fulvestrant with or without palbociclib in preand postmenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer that progressed on prior endocrine therapy – confirmed efficacy and safety. Presented at SABCS-2015, San Antonio, Texas, USA. Abstr. P4-13-01.
32. Turner N.C., Jiang Y., O’Leary B. et al. Efficacy of palbociclib plus fulvestrant (P + F) in patients (pts) with metastatic breast cancer (MBC) and ESR1 mutations (mus) in circulating tumor DNA (ctDNA). J Clin Oncol 2016;34(Suppl);512.
33. Harbeck N., Iyer S., Cristofanilli M. et al. Quality of life with palbociclib plus fulvestrant in previously treated hormone receptorpositive, HER2-negative metastatic breast cancer: patient-reported outcomes from the PALOMA-3 trial. Ann Oncol 2016;27(6):1047–54. PMID: 27029704. DOI: 10.1093/annonc/mdw139.
34. Hortobagyi G.N., Stemmer S.M., Burris H.A. et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med 2016;375(16):1738–48. PMID: 27717303. DOI: 10.1056/NEJMoa1609709.
35. Hortobagyi G.N., Stemmer S.M., Burris H.A. et al. Updated results from MONALEESA-2, a phase 3 trial of firstline ribociclib + letrosol in hormone receptorpositive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC). ASCO-2017. Abstr. 1038.
36. Tripathy D., Sohn J., Im S.A. et al. Firstline ribociclib or placebo combined with goserelin and tamoxifen or non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: results from the randomized phase III MONALEESA-7 trial. Presented at 2017 San Antonio Breast Cancer Symposium, Dec 5–9, 2017, San Antonio, Texas, USA. Abstr. GS2-05.
37. Goetz M.P., Toi M., Campone M. et al. MONARCH-3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol 2017;35(32):3638–46. PMID: 28968163. DOI: 10.1200/JCO.2017.75.6155.
38. Medication package insert for Kisqali® (LP-004670 dated 25.01.2018). (In Russ.).
39. Durairaj C., Ruiz-Garcia A., Gauthier E.R. et al. Palbociclib has no clinically relevant effect on the QTc interval in patients with advanced breast cancer. Anticancer Drugs 2018;29(3):271–80. DOI: 10.1097/CAD.0000000000000589.
40. Sledge G.W., Toi M., Neven P. 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 2017;(25):2874–84. DOI: 10.1200/JCO.2017.73.7585.
41. Costa R., Costa R.B., Talamantes S.M. et al. Meta-analysis of selected toxicity endpoints of CDK4/6 inhibitors: palbociclib and ribociclib. Breast 2017;(35):1–7. DOI: 10.1016/j.breast.2017.05.016.
42. Iacobucci G. NICE recommends routine NHS funding for new breast cancer drugs. BMJ 2017;(359):j5309. DOI: 10.1136/bmj.j5309.
43. Xu W., Mardekian J., Mc-Roy L. et al. Population characteristics and utilization pattern of patients treated with palbociclib over 2 years of postapproval. Presented at SABCS-2017. Abstr. P3-11-08.
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For citations:
Artamonova E.V. PRACTICAL ASPECTS OF ADMINISTERING CYCLIN-DEPENDENT KINASES INHIBITORS: EFFICACY AND TOLERABILITY. Tumors of female reproductive system. 2018;14(1):52-60. (In Russ.) https://doi.org/10.17650/1994-4098-2018-14-1-52-60
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