Real-world Experience with CDK4/6 Inhibitors in Hormone Receptor-positive Metastatic and Recurrent Breast Cancer: Findings from an Asian Population

Overview

Journal Clin Exp Med

Specialty General Medicine

Date 2024 Aug 12

PMID 39133334

Authors

Bo-Fang Chen

Yi-Fang Tsai

Ta-Chung Chao

Pei-Ju Lien

Yen-Shu Lin

Chin-Jung Feng

Yen-Jen Chen

Han-Fang Cheng

Chun-Yu Liu

Jiun-I Lai

Ling-Ming Tseng

Chi-Cheng Huang

Affiliations

Soon will be listed here.

Abstract

Purpose: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy have demonstrated significant clinical benefits in progression-free and overall survival. This study investigates the outcomes associated with two kinds of CDK4/6i in patients with hormone receptor (HR)-positive metastatic and relapsed breast cancer to inform real-world evidence of treatment strategies.

Methods: This retrospective study included 340 Taiwanese patients with HR-positive advanced breast cancer from the Taipei Veterans General Hospital, between 2018 and 2023. We analyzed patient characteristics, treatment strategies and outcomes associated with two CDK4/6i. The efficacy of patients who experienced economic burden and interrupted CDK4/6i treatment after 2 years of National Health Insurance (NHI) reimbursement was also investigated.

Results: Patients receiving ribociclib and palbociclib showed no significant differences in age, histology, body mass index(BMI), or pathologic status. The distribution of disease status and endocrine therapy partners was comparable between the two groups. Dose reduction was similar, while patients with palbociclib tended to discontinue CDK4/6i usage, and those with ribociclib tended to switch to the other CDK4/6i or endocrine partners. There was no significant difference in progression-free survival (PFS) between the two CDK4/6i in the first-line setting. Adverse prognostic factors were increasing HER2 IHC score, higher Ki-67 levels, visceral and liver metastasis, prior chemotherapy, and endocrine therapy resistance, while higher BMI, bone-only metastasis, and letrozole treatment were associated with a lower risk of progression. The limited follow-up time in our study was insufficient to assess the outcomes of patients treated with interrupted CDK4/6i for up to two years under the NHI reimbursement policy.

Conclusion: Treatment outcomes between the two types of CDK4/6i did not differ significantly, indicating the safety and efficacy of CDK4/6i for the Asian population. Ribociclib and palbociclib showed similar efficacy in PFS in the real-world setting.

Citing Articles

Clinical Outcomes of Patients Treated with Ribociclib in Combination with Aromatase Inhibitors or Fulvestrant for HR-Positive, HER2-Negative Metastatic Breast Cancer, Real-World Data from a Low-Resourced Country.

Abdel-Razeq H, Sharaf B, Khater S, Baidoun H, Bani Hani H, Taqash A Immunotargets Ther. 2024; 13:501-512.

PMID: 39364228 PMC: 11448467. DOI: 10.2147/ITT.S479153.

References

De Laurentiis M, Borstnar S, Campone M, Warner E, Salvador Bofill J, Jacot W . Full population results from the core phase of CompLEEment-1, a phase 3b study of ribociclib plus letrozole as first-line therapy for advanced breast cancer in an expanded population. Breast Cancer Res Treat. 2021; 189(3):689-699. PMC: 8505291. DOI: 10.1007/s10549-021-06334-0. View

Ettl J, Im S, Ro J, Masuda N, Colleoni M, Schnell P . Hematologic adverse events following palbociclib dose reduction in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: pooled analysis from randomized phase 2 and 3 studies. Breast Cancer Res. 2020; 22(1):27. PMC: 7068918. DOI: 10.1186/s13058-020-01263-0. View

Hortobagyi G, Stemmer S, Burris H, Yap Y, Sonke G, Hart L . Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer. N Engl J Med. 2022; 386(10):942-950. DOI: 10.1056/NEJMoa2114663. View

Im S, Lu Y, Bardia A, Harbeck N, Colleoni M, Franke F . Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer. N Engl J Med. 2019; 381(4):307-316. DOI: 10.1056/NEJMoa1903765. View

Cuzick J, Dowsett M, Pineda S, Wale C, Salter J, Quinn E . Prognostic value of a combined estrogen receptor, progesterone receptor, Ki-67, and human epidermal growth factor receptor 2 immunohistochemical score and comparison with the Genomic Health recurrence score in early breast cancer. J Clin Oncol. 2011; 29(32):4273-8. DOI: 10.1200/JCO.2010.31.2835. View

McAndrew N, Dickson M, Clark A, Troxel A, OHara M, Colameco C . Early treatment-related neutropenia predicts response to palbociclib. Br J Cancer. 2020; 123(6):912-918. PMC: 7492243. DOI: 10.1038/s41416-020-0967-7. View

Cardoso F, Costa A, Senkus E, Aapro M, Andre F, Barrios C . 3rd ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3). Ann Oncol. 2017; 28(12):3111. PMC: 5834023. DOI: 10.1093/annonc/mdx036. View

Muller C, Kiver V, Solomayer E, Wagenpfeil G, Neeb C, Blohmer J . CDK4/6 Inhibitors in Advanced HR+/HER2 - Breast Cancer: A Multicenter Real-World Data Analysis. Breast Care (Basel). 2023; 18(1):31-41. PMC: 9982335. DOI: 10.1159/000527917. View

Rudmann D . On-target and off-target-based toxicologic effects. Toxicol Pathol. 2012; 41(2):310-4. DOI: 10.1177/0192623312464311. View

10.

Freites-Martinez A, Santana N, Arias-Santiago S, Viera A . Using the Common Terminology Criteria for Adverse Events (CTCAE - Version 5.0) to Evaluate the Severity of Adverse Events of Anticancer Therapies. Actas Dermosifiliogr (Engl Ed). 2020; 112(1):90-92. DOI: 10.1016/j.ad.2019.05.009. View

11.

Rugo H, Liu X, Li B, McRoy L, Chen C, Layman R . Real-world treatment patterns for palbociclib plus an aromatase inhibitor, or an aromatase inhibitor alone, for patients with metastatic breast cancer in the Flatiron Database. Int J Cancer. 2023; 154(4):701-711. DOI: 10.1002/ijc.34748. View

12.

de Lusignan S, Crawford L, Munro N . Creating and using real-world evidence to answer questions about clinical effectiveness. J Innov Health Inform. 2015; 22(3):368-73. DOI: 10.14236/jhi.v22i3.177. View

13.

Gennari A, Andre F, Barrios C, Cortes J, de Azambuja E, DeMichele A . ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer. Ann Oncol. 2021; 32(12):1475-1495. DOI: 10.1016/j.annonc.2021.09.019. View

14.

Buller W, Pallan L, Chu T, Khoja L . CDK4/6 inhibitors in metastatic breast cancer, a comparison of toxicity and efficacy across agents in a real-world dataset. J Oncol Pharm Pract. 2023; 29(8):1825-1835. DOI: 10.1177/10781552231163121. View

15.

Rugo H, Brufsky A, Liu X, Li B, McRoy L, Chen C . Real-world study of overall survival with palbociclib plus aromatase inhibitor in HR+/HER2- metastatic breast cancer. NPJ Breast Cancer. 2022; 8(1):114. PMC: 9553912. DOI: 10.1038/s41523-022-00479-x. View

16.

Torregrosa-Maicas M, Del Barco-Berron S, Cotes-Sanchis A, Lema-Roso L, Servitja-Tormo S, Girones-Sarrio R . Expert consensus to optimize the treatment of elderly patients with luminal metastatic breast cancer. Clin Transl Oncol. 2022; 24(6):1033-1046. PMC: 9107453. DOI: 10.1007/s12094-021-02766-8. View

17.

Franzoi M, Eiger D, Ameye L, Ponde N, Caparica R, De Angelis C . Clinical Implications of Body Mass Index in Metastatic Breast Cancer Patients Treated With Abemaciclib and Endocrine Therapy. J Natl Cancer Inst. 2020; 113(4):462-470. PMC: 8023855. DOI: 10.1093/jnci/djaa116. View

18.

Hortobagyi G, Stemmer S, Burris H, Yap Y, Sonke G, Paluch-Shimon S . Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer. N Engl J Med. 2016; 375(18):1738-1748. DOI: 10.1056/NEJMoa1609709. View

19.

Turner N, Slamon D, Ro J, Bondarenko I, Im S, Masuda N . Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer. N Engl J Med. 2018; 379(20):1926-1936. DOI: 10.1056/NEJMoa1810527. View

20.

Olsson L, Walens A, Hamilton A, Benefield H, Fleming J, Carey L . Obesity and Breast Cancer Metastasis across Genomic Subtypes. Cancer Epidemiol Biomarkers Prev. 2022; 31(10):1944-1951. PMC: 9628732. DOI: 10.1158/1055-9965.EPI-22-0013. View