Prospects of eribulin administration for patients with HR-positive HER2-negative metastatic breast cancer after progression on CDK4/6 Inhibitors: theoretical background and first experience

Cover Page

Cite item

Abstract

Combining cyclin-dependent kinases 4 and 6 (CDK 4/6) inhibitors with endocrine therapies in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer in the first and second lines has emerged as optimal treatment strategy and has implications related to clinical efficacy, rapid clinical response and manageable tolerability. However, approximately one in five women has progression during the first year, we have to make efforts to choose the treatments for hormone receptor-positive breast cancer. Potential treatment options include prospective chemotherapy drug eribulin, its efficacy has been demonstrated in various biological subtypes of metastatic breast cancer in patients pretreated with anthracyclines and taxanes. Data from EMPOWER study evaluating the use of eribulin in female patients with hormone positive HER2-negative metastatic breast cancer who received CDK 4/6 inhibitor therapy showed promising results. In the cohort eribulin was prescribed according to the FDA indications in the USA after at least three prior regimens with a prior anthracycline and a taxane overall response rate was 26.7%, clinical benefit rate was 54.1%, median progressive-free survival was not reached and 6-month progressive-free survival rates was 70.4%. Eribulin demonstrated a manageable tolerability profile, adverse event rates were similar to those in clinical trials and other observational studies. In this paper we present the analysis from Russia of five cases of luminal HER2-negative breast cancer who had progression after CDK 4/6 inhibitor therapy. All patients had visceral metastases, one of them had brain metastases. Eribulin was used according to prescribing information in Russia, in metastatic settings in patients pretreated with anthracyclines and taxanes in the second chemotherapy line (3 patients) and in the third line (2 patients). Four patients achieved stable disease, one patient had partial response. Duration of eribulin treatment response was from 8 to 22 months. Eribulin appeared to be well-tolerated, dose reduction was not noted. Data from EMPOWER (USA) and the first treatment results from Russia demonstrated eribulin may be a potential treatment option in hormone-positive breast cancer following prior CDK 4/6i therapy for disease control and to preserve quality of life.

About the authors

Irina V. Kolyadina

Russian Medical Academy of Continuous Professional Education

Author for correspondence.
Email: irinakolyadina@yandex.ru
ORCID iD: 0000-0002-1124-6802

MD, PhD, Prof.

Russian Federation, Moscow

Inna P. Ganshina

Blokhin National Medical Research Center of Oncology

Email: irinakolyadina@yandex.ru

Leading Researcher Officer

Russian Federation, Moscow

Svetlana V. Kuzmicheva

Loginov Moscow Clinical Scientific Center

Email: irinakolyadina@yandex.ru

head of the day hospital

Russian Federation, Moscow

Asiiat I. Tekeeva

Rehabilitation Medical Center

Email: irinakolyadina@yandex.ru

oncologist

Russian Federation, Podolsk

James D. Kolokolov

Botkin City Clinical Hospital

Email: irinakolyadina@yandex.ru

chemotherapist

Russian Federation, Moscow

Mikhail V. Volkonskii

Moscow City Oncological Hospital №62

Email: irinakolyadina@yandex.ru
ORCID iD: 0000-0003-4060-5015

head of the day hospital

Russian Federation, Istra

Irina V. Poddubnaya

Russian Medical Academy of Continuous Professional Education

Email: irinakolyadina@yandex.ru
ORCID iD: 0000-0002-0995-1801

D. Sci. (Med.), Prof., Acad. RAS

Russian Federation, Moscow

References

  1. https://www.iarc.fr/infographics/globocan-2018-latest-global-cancer-data/
  2. Состояние онкологической помощи населению России в 2018 году. Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Петровой. М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2019. [The status of cancer care for the population of Russia in 2018. Ed. A.D. Kaprin,, V.V. Starinsky, G.V. Petrova. Moscow: MNIOI im. P.A. Gertsena – filial FGBU «NMITs radiologii’ Minzdrava Rossii, 2019 (in Russian).]
  3. Yersa O et al. Biological subtypes of breast cancer: Prognostic and therapeutic implications. World J Clin Oncol 2014; 5 (3): 412–24.
  4. Migliaccio I. Endocrine therapy considerations in postmenopausal patients with hormone receptor positive, human epidermal growth factor receptor type 2 negative advanced breast cancers. BMC Med 2015; 13: 46.
  5. Филоненко Д.А., Ганьшина И.П., Кондратьева О.Е. и др. Особенности метастазирования долькового рака молочной железы. Акушерство и гинекология. 2019; 10: 180–7. [Filonenko D.A., Gan’shina I.P., Kondrat’eva O.E. et al. Osobennosti metastazirovaniia dol’kovogo raka molochnoi zhelezy. Akusherstvo i ginekologiia. 2019; 10: 180–7 (in Russian).]
  6. Bonotto M, Gerratana L, Di Maio M et al. Chemotherapy versus endocrine therapy as first-line treatment in patients with luminal-like HER2-negative metastatic breast cancer: A propensity score analysis. Breast 2017; 31: 114–20. doi: 10.1016/j.breast.2016.10.021
  7. 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. Lancet 2016; 388 (10063): 2997–3005. doi: 10.1016/S0140-6736(16)32389-3
  8. Yardley DA, Chan A, Nusch A et al. Ribociclib + endocrine therapy in patients with hormone receptor-positive, HER2-negative advanced breast cancer presenting with visceral metastases: subgroup analysis of phase III MONALEESA trials. Paper presented at: San Antonio Breast Cancer Symposium; December 4–8, 2018; San Antonio, TX. Abstract 1000.
  9. Bardia A et al. Tamoxifen or a nonsteroidal aromatase inhibitor with ribociclib in premenopausal patients with hormone receptor-positive, HER2-negative advanced breast cancer: MONALEESA-7 subgroup analysis. Poster presented at: European Society for Medical Oncology Congress; October 19–23, 2018; Munich, Germany. Poster 330P.
  10. Ганьшина И.П., Филоненко Д.А., Гордеева О.О. и др. Рибоциклиб в лечении гормонопозитивного HER2-негативного рака молочной железы. Мед. совет. 2019; 10: 72–80. [Gan’shina I.P., Filonenko D.A., Gordeeva O.O. et al. Ribotsiklib v lechenii gormonopozitivnogo HER2-negativnogo raka molochnoi zhelezy. Med. sovet. 2019; 10: 72–80. (in Russian).]
  11. Rugo HS, Finn RS, Gelmon K et al. Progression-free Survival Outcome Is Independent of Objective Response in Patients With Estrogen Receptor-positive, Human Epidermal Growth Factor Receptor 2-negative Advanced Breast Cancer Treated With Palbociclib Plus Letrozole Compared With Letrozole: Analysis From PALOMA-2. Clin Breast Cancer 2020; 20 (2): e173–e180. doi: 10.1016/j.clbc.2019.08.009
  12. Finn RS, Crown JP, 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 the randomized pivotal trial PALOMA-1/TRIO-18. Breast Cancer Res 2016; 18 (1): 67. doi: 10.1186/s13058-016-0721-5
  13. Hortobagyi GN, Stemmer SM, Burris HA 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. doi: 10.1093/annonc/mdy155
  14. Im SA, Lu YS, Bardia A et al. Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer. N Engl J Med 2019; 381 (4): 307–16. doi: 10.1056/NEJMoa1903765
  15. Sledge GW Jr, Toi M, Neven P 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 2019. doi: 10.1001/jamaoncol.2019.4782
  16. Iorfida M, Mazza M, Munzone E et al. Fulvestrant in Combination with CDK4/6 Inhibitors for HER2- Metastatic Breast Cancers: Current Perspectives. Breast Cancer (Dove Med Press). 2020; 12: 45–56. doi: 10.2147/BCTT.S196240
  17. 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.
  18. Стенина М.Б., Жукова Л.Г., Королева И.А. и др. Практические рекомендации по лекарственному лечению инвазивного рака молочной железы. DOI: 10.18027 / 2224-5057-2019-9-3s2-128-163. https://rosoncoweb.ru/standarts/RUSSCO/2019/2019-08.pdf [Stenina M.B., Zhukova L.G., Koroleva I.A. et al. Prakticheskie rekomendatsii po lekarstvennomu lecheniiu invazivnogo raka molochnoi zhelezy. DOI: 10.18027 / 2224-5057-2019-9-3s2-128-163. https://rosoncoweb.ru/standarts/RUSSCO/2019/2019-08.pdf (in Russian).]
  19. Princic N, Aizer A, Tang DH et al. Predictors of systemic therapy sequences following a CDK 4/6 inhibitor-based regimen in post-menopausal women with hormone receptor positive, HEGFR-2 negative metastatic breast cancer. Curr Med Res Opin 2018; 35 (1): 73–80.
  20. Горбунова В.А., Колядина И.В., Коваленко Е.И. и др. Эффективность и безопасность эрибулина при HER2-отрицательном метастатическом раке молочной железы: данные многолетнего опыта из реальной клинической практики в России. Современная Онкология. 2019; 21 (1): 12–23. doi: 10.26442/18151434.2019.1.190250 [Gorbunova V.A., Kolyadina I.V., Kovalenko E.I. et al. Efficacy and safety of eribulin in HER2-negative metastatic breast cancer: the results of long-term experience in real clinical practice in Russia. Journal of Modern Oncology. 2019; 21 (1): 12–23. doi: 10.26442/18151434.2019.1.190250 (in Russian).]
  21. Cortes J, Schoffski P, Littlefield B. Multiple modes of action of eribulin mesylate: Emerging data and clinical implication. Cancer Treat Rev 2018; 70: 190–8.
  22. Cortes J, O’Shaughnessy J, Loesch D et al. Eribulin monotherapy versus treatment of physician’s choice in patients with metastatic breast cancer (EMBRACE): a Phase 3 open-label randomised study. Lancet 2011; 377 (9769): 914–23.
  23. Pivot X. Pooled analyses of eribulin in metastatic breast cancer patients with at least one prior chemotherapy. Ann Oncology 2016. doi: 10.1093/annonc/mdw203
  24. Pivot X, Seock Ah Im, Guo M, Marm F. Subgroup analysis of patients with HER2 negative metastatic Breast Cancer in the second line setting from a phase 3, open label, randomized study of eribulin mesilate versus capecitabine. Breast Cancer 2018; 25 (3): 370–4. doi: 10.1007/s12282-017-0826-4
  25. Mougalian SS, Feinberg BA, Wang E et al. Observational study of clinical outcomes of eribulin mesylate in metastatic breast cancer after cyclin-dependent kinase 4/6 inhibitor therapy. Future Oncol 2019; 15 (34): 3935–44.

Supplementary files

Supplementary Files
Action
1. JATS XML
2. Fig. 1. The efficacy of eribulin as the 3rd line of chemotherapy in a patient with HR-positive HER2-negative metastatic breast cancer, before the start of an eribulin therapy and after 11 months of the therapy.

Download (477KB)
3. Fig. 2. Metastases in the frontal bone, cerebral membranes with intracranial component (a – before the eribulin therapy, b – after 10 cycles of eribulin).

Download (259KB)

Copyright (c) 2020 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
 


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies