Optimizing Quality of Life in Patients with Hormone Receptor-Positive Metastatic Breast Cancer: Treatment Options and Considerations

215 Background: Molecular heterogeneity in breast cancer has led to increasing attention in the role of cell cycle signaling especially the cyclins and their associated proteins, cycle-dependent kinases (CDK), in carcinogenesis and treatment resistance in hormone receptor-positive metastatic breast cancer. Many CDK 4/6 agents have been proven beneficial. Nevertheless, health-related quality of life from pain and fatigue remains a concern. We performed a systematic review and meta-analysis of randomized controlled trials (RCT) to determine these risks. Methods: MEDLINE, EMBASE databases and meeting abstracts from inception through June 2017 were queried. RCTs that mention back pain, pain in arms and legs, arthralgia and fatigue as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio with 95% confidence interval (CI). Random effects model was applied. Results: A total of 2671 patients with hormone receptor-positive HER2-negative metastatic breast cancer from four phase 3 studies and one phase 2 study were eligible for analysis. The study arms used palbociclib-letrozole, palbociclib-fulvestrant, ribociclib-letrozole and abemaciclib-fulvestrant while the control arms utilized placebo in combination with letrozole or fulvestrant. The relative risk (RR) of all-grade back pain was 0.97 (95% CI: 0.81- 1.16; p = 0.76); all-grade pain in arms and legs was 0.98 (95% CI: 0.74- 1.30; p = 0.90); all-grade arthralgia was 0.98 (95% CI: 0.75- 1.27; p = 0.88); and all-grade fatigue was 1.35 (95% CI: 1.20- 1.52; p < 0.0001). The RR of high-grade back pain was 1.47 (95% CI: 0.51- 4.23; p = 0.46); high-grade pain in arms and legs was 0.12 (95% CI: 0.02- 0.73; p = 0.02); high-grade arthralgia was 1.14 (95% CI: 0.40- 3.26; p = 0.79); and high-grade fatigue was 3.06 (95% CI: 1.41- 6.61; p = 0.004). Conclusions: Patients on CDK4/6 inhibitor-based regimens experienced a significant increase in all-grades of fatigue with a relative risk of 3.06 for grade 3 and 4 fatigue whereas they noted a decrease in high-grade pain in the arms and legs favoring CDK 4/6 inhibitor based regimens.

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CDK4/6 Inhibitors in Hormone Receptor-Positive Metastatic Breast Cancer: Current Practice and Knowledge

Cancers ◽

10.3390/cancers12092480 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2480

Author(s):

Debora de Melo Gagliato ◽

Antonio C Buzaid ◽

Jose Manuel Perez-Garcia ◽

Antonio Llombart ◽

Javier Cortes

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Hormone Receptor ◽

Current Knowledge ◽

Metastatic Breast ◽

Endocrine Treatment ◽

Cyclin Dependent Kinase ◽

Hormone Receptor Positive ◽

Positive Breast Cancer

Treatment paradigms in advanced hormone receptor (HR)-positive breast cancer were substantially transformed with cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) approval. The addition of these drugs to endocrine treatment profoundly improved progression-free and overall survival. Additionally, other important endpoints, such as the response rate, time to chemotherapy, and a delay in quality of life deterioration, were positively impacted by CDK4/6 inhibitors’ addition to the treatment of advanced HR-positive breast cancer. This review article will summarize current knowledge on CDK4/6 inhibitors in clinical practice for advanced HR-positive metastatic breast cancer, as well as describe recent efforts to more precisely characterize mechanisms of sensitivity and resistance to these drugs, both on the molecular and clinical characterization level.

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Ribociclib and Abemaciclib: CDK4/6 Inhibitors for the Treatment of Hormone Receptor–Positive Metastatic Breast Cancer

Journal of the Advanced Practitioner in Oncology ◽

10.6004/jadpro.2021.12.1.8 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Kristina F. Byers, PharmD, BCOP

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Hormone Receptor ◽

Oral Treatment ◽

Treatment Options ◽

Metastatic Breast ◽

Phase Iii ◽

Breast Cancers ◽

Cancer Data ◽

Hormone Receptor Positive

The treatment landscape of hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) metastatic breast cancer has been modernized by the identification of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. Because the majority of HR+ breast cancers will develop resistance to endocrine therapies (tamoxifen and aromatase inhibitors), newer treatment options are necessary to restore endocrine sensitivity and prolong survival. Ribociclib and abemaciclib are two of three CDK4/6 inhibitors currently approved for first- and second-line treatment of HR+/HER2– metastatic breast cancer. Data from large, phase III clinical trials have demonstrated an improvement in both progression-free and overall survival with the addition of ribociclib or abemaciclib to endocrine-based therapy, establishing a new frontline standard of care. Treatment with ribociclib and abemaciclib provide a convenient oral treatment option that is both efficacious and well tolerated.

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