CDK4/6 inhibitors: The Devil is in the Detail

Finn RS, Martin M, Rugo HS, Jones S, Im SA, Gelmon K, et al. Palbociclib and Letrozole in Advanced Breast Cancer. N Engl J Med. 2016;375(20):1925–36. https://doi.org/10.1056/NEJMoa1607303.

Article  CAS  PubMed  Google Scholar 

Turner NC, Ro J, André F, Loi S, Verma S, Iwata H, et al. Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2015;373(3):209–19. https://doi.org/10.1056/NEJMoa1505270.

Article  CAS  PubMed  Google Scholar 

Turner NC, Slamon DJ, Ro J, Bondarenko I, Im SA, Masuda N, et al. Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer. N Engl J Med. 2018;379(20):1926–36. https://doi.org/10.1056/NEJMoa1810527.

Article  CAS  PubMed  Google Scholar 

Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, et al. Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer. N Engl J Med. 2016;375(18):1738–48. https://doi.org/10.1056/NEJMoa1609709.

Article  CAS  PubMed  Google Scholar 

Johnston S, Martin M, Di Leo A, Im SA, Awada A, Forrester T, et al. MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer. NPJ Breast Cancer. 2019;5:5. https://doi.org/10.1038/s41523-018-0097-z.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tripathy D, Im SA, Colleoni M, Franke F, Bardia A, Harbeck N, et al. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol. 2018;19(7):904–15. https://doi.org/10.1016/S1470-2045(18)30292-4.

Article  CAS  PubMed  Google Scholar 

Sledge GW, Toi M, Neven P, Sohn J, Inoue K, Pivot X, 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;35(25):2875–84. https://doi.org/10.1200/JCO.2017.73.7585.

Article  CAS  PubMed  Google Scholar 

Slamon DJ, Neven P, Chia S, Fasching PA, De Laurentiis M, Im SA, et al. 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. 2018;36(24):2465–72. https://doi.org/10.1200/JCO.2018.78.9909.

Article  CAS  PubMed  Google Scholar 

•Johnston SRD, Harbeck N, Hegg R, Toi M, Martin M, Shao ZM, et al. Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2-, Node-Positive, High-Risk, Early Breast Cancer (monarchE). J Clin Oncol. 2020 Dec 1;38(34):3987–98. https://doi.org/10.1200/JCO.20.02514. The initial results of the phase 3 monarchE trial were presented in this article. This study showed that the addition of 2 years of abemaciclib to standard adjuvant ET resulted in significant improvement in iDFS in patients with high-risk HR+/HER2- eBC.

Ding L, Cao J, Lin W, Chen H, Xiong X, Ao H, et al. The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer. Int J Mol Sci. 2020;21(6):1960. https://doi.org/10.3390/ijms21061960.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Malumbres M, Barbacid M. To cycle or not to cycle: a critical decision in cancer. Nat Rev Cancer. 2001;1(3):222–31. https://doi.org/10.1038/35106065.

Article  CAS  PubMed  Google Scholar 

Santo L, Siu KT, Raje N. Targeting Cyclin-Dependent Kinases and Cell Cycle Progression in Human Cancers. Semin Oncol. 2015;42(6):788–800. https://doi.org/10.1053/j.seminoncol.2015.09.024.

Article  CAS  PubMed  Google Scholar 

Arnold A, Papanikolaou A. Cyclin D1 in breast cancer pathogenesis. J Clin Oncol. 2005;23(18):4215–24. https://doi.org/10.1200/JCO.2005.05.064.

Article  CAS  PubMed  Google Scholar 

Network CGA. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61–70. https://doi.org/10.1038/nature11412.

Article  CAS  Google Scholar 

Fornier MN, Rathkopf D, Shah M, Patil S, O’Reilly E, Tse AN, et al. Phase I dose-finding study of weekly docetaxel followed by flavopiridol for patients with advanced solid tumors. Clin Cancer Res. 2007;13(19):5841–6. https://doi.org/10.1158/1078-0432.CCR-07-1218.

Article  CAS  PubMed  Google Scholar 

Marra A, Curigliano G. Are all cyclin-dependent kinases 4/6 inhibitors created equal? NPJ Breast Cancer. 2019;5:27. https://doi.org/10.1038/s41523-019-0121-y.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen P, Lee NV, Hu W, Xu M, Ferre RA, Lam H, et al. Spectrum and Degree of CDK Drug Interactions Predicts Clinical Performance. Mol Cancer Ther. 2016;15(10):2273–81. https://doi.org/10.1158/1535-7163.MCT-16-0300.

Article  CAS  PubMed  Google Scholar 

Gelbert LM, Cai S, Lin X, Sanchez-Martinez C, Del Prado M, Lallena MJ, et al. Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine. Invest New Drugs. 2014;32(5):825–37. https://doi.org/10.1007/s10637-014-0120-7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Corona SP, Generali D. Abemaciclib: a CDK4/6 inhibitor for the treatment of HR+/HER2- advanced breast cancer. Drug Des Devel Ther. 2018;12:321–30. https://doi.org/10.2147/DDDT.S137783.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Asghar U, Witkiewicz AK, Turner NC, Knudsen ES. The history and future of targeting cyclin-dependent kinases in cancer therapy. Nat Rev Drug Discov. 2015;14(2):130–46. https://doi.org/10.1038/nrd4504.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009;9(3):153–66. https://doi.org/10.1038/nrc2602.

Article  CAS  PubMed  Google Scholar 

George MA, Qureshi S, Omene C, Toppmeyer DL, Ganesan S. Clinical and Pharmacologic Differences of CDK4/6 Inhibitors in Breast Cancer. Front Oncol. 2021;12(11): 693104. https://doi.org/10.3389/fonc.2021.693104.

Article  CAS  Google Scholar 

Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, 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. Ann Oncol. 2018;29(7):1541–7. https://doi.org/10.1093/annonc/mdy155.

Article  CAS  PubMed  Google Scholar 

Schaeffer S, Lutz C, Dobbie M, Terracciano LM, Matter M, Vosbeck J, et al. Ribociclib-induced liver injury: a case report. Front Oncol. 2023;13:1256783. https://doi.org/10.3389/fonc.2023.1256783.

Article  PubMed  PubMed Central  Google Scholar 

Wani K, Patel K, Dabak V. Hepatotoxicity After CDK 4/6 Inhibitor Initiation in the Treatment of Hormone-Positive Metastatic Breast Cancer. Cureus. 15(6):e40871. https://doi.org/10.7759/cureus.40871

Chappell JC, Turner PK, Pak YA, Bacon J, Chiang AY, Royalty J, et al. Abemaciclib Inhibits Renal Tubular Secretion Without Changing Glomerular Filtration Rate. Clin Pharmacol Ther. 2019;105(5):1187–95. https://doi.org/10.1002/cpt.1296.

Article  CAS  PubMed  Google Scholar 

Patnaik A, Rosen LS, Tolaney SM, Tolcher AW, Goldman JW, Gandhi L, et al. Efficacy and Safety of Abemaciclib, an Inhibitor of CDK4 and CDK6, for Patients with Breast Cancer, Non-Small Cell Lung Cancer, and Other Solid Tumors. Cancer Discov. 2016;6(7):740–53. https://doi.org/10.1158/2159-8290.CD-16-0095.

Article  CAS  PubMed  Google Scholar 

Dickler MN, Tolaney SM, Rugo HS, Cortés J, Diéras V, Patt D, et al. MONARCH 1, A Phase II Study of Abemaciclib, a CDK4 and CDK6 Inhibitor, as a Single Agent, in Patients with Refractory HR+/HER2- Metastatic Breast Cancer. Clin Cancer Res. 2017;23(17):5218–24. https://doi.org/10.1158/1078-0432.CCR-17-0754.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, et al. The Effect of Abemaciclib Plus Fulvestrant on Overall Survival in Hormone Receptor-Positive, ERBB2-Negative Breast Cancer That Progressed on Endocrine Therapy—MONARCH 2: A Randomized Clinical Trial. JAMA Oncol. 2020;6(1):116–24. https://doi.org/10.1001/jamaoncol.2019.4782.

Article  PubMed  Google Scholar 

•• Goetz M, Toi M, Huober J, Sohn JH, Tredan O, Park IH, et al. (GS01–12) MONARCH 3: Final overall survival results of abemaciclib plus a nonsteroidal aromatase inhibitor as first-line therapy for HR+, HER2- advanced breast cancer [Internet]. Oral presentation presented at: San Antonio Breast Cancer Symposium 2023; 2023 Dec 6 [cited 2023 Dec 29]; San Antonio, TX. Available from: https://sabcs2023.eventscribe.net/fsPopup.asp?PresentationID=1329789&returl=YWpheGNhbGxzL3Nlc3Npb25pbmZvLmFzcD9QcmVzZW50YXRpb25JRD0xMzM2NzI3&mode=presInfo. Accessed 29 Dec 2023. Final OS results of the MONARCH-3 trial were presented at the San Antonio Breast Cancer Symposium in December 2023 which showed a clinically meaningful but statistically not significant improvement in median OS with the addition of abemaciclib to NSAI as first line therapy in HR+/HER2- mBC.

••Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Hart L, et al. Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer. N Engl J Med. 2022 Mar 10;386(10):942–50. https://doi.org/10.1056/NEJMoa2114663. Overall survival results from the phase 3 MONALEESA-2 trial, which showed statistically significant prolongation of OS with the addition of ribociclib to letrozole in the first line treatment of HR+/HER2- mBC. Given the consistent OS benefits seen across the MONALEESA trials, ribociclib is now the preferred first line CDK4/6i based on category 1 NCCN recommendations.

••Slamon DJ, Neven P, Chia S, Jerusalem G, De Laurentiis M, Im S, et al. 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. Ann Oncol. 2021 Aug;32(8):1015–24. https://doi.org/10.1016/j.annonc.2021.05.353. Updated OS results of MONALEESA-3, which showed OS improvement with the addition of ribociclib to fulvestrant in 1st and 2nd line treatment of HR+/HER2- mBC.

Im SA, Lu YS, Bardia A, Harbeck N, Colleoni M, Franke F, et al. Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer. N Engl J Med. 2019;381(4):307–16. https://doi.org/10.1056/NEJMoa1903765.

Article  CAS  PubMed  Google Scholar 

••Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.5.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed [December 22, 2023]. To view the most recent and complete version of the guideline, go online to NCCN.org. Most recent update to the NCCN Breast Cancer Guidelines includes a category 1 recommendation for the use of ribociclib in combination with ET for the first line treatment of HR+/HER2- mBC.

Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, 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. https://doi.org/10.1016/S1470-2045(14)71159-3.

Article  CAS  PubMed 

留言 (0)

沒有登入
gif