CDK4/6 inhibitors; HR-positive/HER2-negative breast cancer; aromatase inhibitors; breast cancer; chemotherapy; endocrine resistance; endocrine therapy; metastatic breast cancer; oncology
Abstract :
[en] In December 2017, ESMO Open-Cancer Horizons convened a round-table discussion on the background and latest data regarding cyclin-dependent kinase (CDK)4/6 inhibitors with endocrine therapy (ET) in the treatment of endocrine-sensitive breast cancer (BC). A review on this discussion was published in summer 2018 (https://esmoopen.bmj.com/content/3/5/e000368).Endocrine-sensitive BC with non-visceral disease and limited spread of the metastases.Endocrine-sensitive BC with non-life-threatening visceral involvement. Several open questions were identified, which led to a second ESMO Open discussion on CDK4/6 inhibitors, taking place in December 2018 and covered in this article. The panel discussed two important clinical scenarios and the pro and cons of a treatment approach with CDK4/6 inhibitors for each scenario:Endocrine-sensitive BC with non-visceral disease and limited spread of the metastases.Endocrine-sensitive BC with non-life-threatening visceral involvement. Regarding scenario 1, the panel agreed that CDK4/6 inhibitors should be recommended in first-line therapy for most patients if cost and practicality allow. However, the use of single-agent ET with an aromatase inhibitor in the first-line treatment of these patients is still a possibility for a small group of patients with very limited disease, such as one or two bone lesions or limited lymph node involvement. Regarding scenario 2, chemotherapy is the first approach for patients with endocrine-sensitive metastatic BC with life-threatening visceral involvement because of the need for a faster response. The therapeutic approaches for patients with non-life-threatening visceral involvement are still under debate. Nevertheless, CDK4/6 inhibitors are currently the treatment of choice for most patients with a close follow-up of tumour response. A treatment algorithm has been suggested at the round table.
Disciplines :
Oncology
Author, co-author :
Awada, Ahmad
Gligorov, Joseph
Jerusalem, Guy ; Université de Liège - ULiège > Département des sciences cliniques > Oncologie
Preusser, Matthias
Singer, Christian
Zielinski, Christoph
Language :
English
Title :
CDK4/6 inhibition in low burden and extensive metastatic breast cancer: summary of an ESMO Open-Cancer Horizons pro and con discussion.
Publication date :
2019
Journal title :
ESMO Open
eISSN :
2059-7029
Publisher :
BMJ Publishing Group, United Kingdom
Volume :
4
Issue :
6
Pages :
e000565
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
(c) Author (s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.
Finn RS, Martin M, Rugo HS, et al. Palbociclib and letrozole in advanced breast cancer. N Engl J Med Overseas Ed 2016;375:1925-36.
Hortobagyi GN, Stemmer SM, Burris HA, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med Overseas Ed 2016;375:1738-48.
Goetz MP, Toi M, Campone M, et al. Monarch 3: Abemaciclib as initial therapy for advanced breast cancer. JCO 2017;35:3638-46.
Preusser M, De Mattos-Arruda L, Thill M, et al. Cdk4/6 inhibitors in the treatment of patients with breast cancer: summary of a multidisciplinary round-table discussion. ESMO Open 2018;3.
Tripathy D, Im S-A, Colleoni M, 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;19:904-15.
Verma S, O'Shaughnessy J, Burris HA, et al. Health-related quality of life of postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer treated with ribociclib + letrozole: results from MONALEESA-2. Breast Cancer Res Treat 2018;170:535-45.
Sonke GS, Hart LL, Campone M, et al. Ribociclib with letrozole vs letrozole alone in elderly patients with hormone receptor-positive, HER2-negative breast cancer in the randomized MONALEESA-2 trial. Breast Cancer Res Treat 2018;167:659-69.
Freedman RA, Tolaney SM. Efficacy and safety in older patient subsets in studies of endocrine monotherapy versus combination therapy in patients with HR+/HER2-advanced breast cancer: a review. Breast Cancer Res Treat 2018;167:607-14.
Rugo HS, Diéras V, Gelmon KA, et al. Impact of palbociclib plus letrozole on patient-reported health-related quality of life: results from the PALOMA-2 trial. Ann Oncol 2018;29:888-94.
Cristofanilli M, Turner NC, 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;17:425-39.
Im S-A, Lu Y-S, Bardia A, et al. Overall survival with Ribociclib plus endocrine therapy in breast cancer. N Engl J Med 2019;381:307-16.
Rugo HS, Rumble RB, Macrae E, et al. Endocrine therapy for hormone Receptor-Positive metastatic breast cancer: American Society of clinical oncology guideline. JCO 2016;34:3069-103.
Cardoso F, Senkus E, Costa A, et al. 4th ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4). Ann Oncol 2018;29:1634-57.
Gradishar WJ, Anderson BO, Balassanian R, et al. Breast cancer, version 4.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 2018;16:310-20.
Slamon DJ, Neven P, Chia S, 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. JCO 2018;36:2465-72.
Sledge GW, 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. JCO 2017;35:2875-84.
Di Leo A, O'Shaughnessy J, Sledge GW, et al. Prognostic characteristics in hormone receptor-positive advanced breast cancer and characterization of abemaciclib efficacy. NPJ Breast Cancer 2018;4.
Robertson JFR, Bondarenko IM, Trishkina E, et al. Fulvestrant 500 Mg versus anastrozole 1 Mg for hormone receptor-positive advanced breast cancer (falcon): an international, randomised, double-blind, phase 3 trial. The Lancet 2016;388:2997-3005.
Bergh J, Jönsson P-E, Lidbrink EK, et al. Fact: an open-label randomized phase III study of fulvestrant and anastrozole in combination compared with anastrozole alone as first-line therapy for patients with receptor-positive postmenopausal breast cancer. JCO 2012;30:1919-25.
Johnston SR, Kilburn LS, Ellis P, et al. Fulvestrant plus anastrozole or placebo versus exemestane alone after progression on non-steroidal aromatase inhibitors in postmenopausal patients with hormone-receptor-positive locally advanced or metastatic breast cancer (SoFEA): a composite, multicentre, phase 3 randomised trial. Lancet Oncol 2013;14:989-98.
Mehta RS, Barlow WE, Albain KS, et al. Overall survival with fulvestrant plus anastrozole in metastatic breast cancer. N Engl J Med 2019;380:1226-34.
Turner NC, Slamon DJ, Ro J, et al. Overall survival with Palbociclib and fulvestrant in advanced breast cancer. N Engl J Med 2018;379:1926-36.
Thill M, Schmidt M. Management of adverse events during cyclin-dependent kinase 4/6 (CDK4/6) inhibitor-based treatment in breast cancer. Ther Adv Med Oncol 2018;10:175883591879332.
Rugo HS, Barry WT, Moreno-Aspitia A, et al. Randomized phase III trial of paclitaxel once per week compared with nanoparticle albumin-bound nab-paclitaxel once per week or ixabepilone with bevacizumab as first-line chemotherapy for locally recurrent or metastatic breast cancer: CALGB 40502/NCCTG N063H (Alliance). JCO 2015;33:2361-9.
Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 2007;357:2666-76.
O'Brien MERet al. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYXTM/ Doxil") versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Annals of Oncology 2004;15:440-9.
Kaufman PA, Awada A, Twelves C, et al. Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane. JCO 2015;33:594-601.
Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 2012;366:520-9.
André F, Ciruelos E, Rubovszky G, et al. Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med 2019;380:1929-40.
Laufman LR, Spiridonidis CH, Pritchard J, et al. Monthly docetaxel and Weekly gemcitabine in metastatic breast cancer: a phase II trial. Ann Oncol 2001;12:1259-64.
Palmeri S, Vaglica M, Spada S, et al. Weekly docetaxel and gemcitabine as first-line treatment for metastatic breast cancer: results of a multicenter phase II study. Oncology 2005;68:438-45.
Turner NC, Finn RS, Martin M, et al. Clinical considerations of the role of palbociclib in the management of advanced breast cancer patients with and without visceral metastases. Ann Oncol 2018;29:669-80.
Lindström LS, Karlsson E, Wilking UM, et al. Clinically used breast cancer markers such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 are unstable throughout tumor progression. JCO 2012;30:2601-8.
Kobayashi K, Ito Y, Ogiya A, et al. Relationship of Ki-67 proliferative index and metastatic tumor of breast cancer. J of Clin Oncol 2017;31.
Cianfrocca M, Goldstein LJ. Prognostic and predictive factors in early-stage breast cancer. Oncologist 2004;9:606-16.
Nienhuis HH, van Kruchten M, Elias SG, et al. 18F-Fluoroestradiol Tumor Uptake Is Heterogeneous and Influenced by Site of Metastasis in Breast Cancer Patients. J Nucl Med 2018;59:1212-8.
O'Shaughnessy J, Goetz MP, Sledge GW, et al. The benefit of abemaciclib in prognostic subgroups: An update to the pooled analysis of MONARCH 2 and 3 [abstract]. In: Proceedings of the American association for cancer research annual meeting 2018. Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018, 2018Apr 14-18.
