J Breast Cancer.  2022 Aug;25(4):296-306. 10.4048/jbc.2022.25.e34.

Time to Chemotherapy for Patients With Estrogen Receptor-Positive Breast Cancer and Cyclin-Dependent Kinase 4 and 6 Inhibitor Use

• Endo Y
• Yoshimura A
• Sawaki M
• Hattori M
• Kotani H
• Kataoka A
• Horisawa N
• Ozaki Y
• Nozawa K
• Takatsuka D
• Isogai A
• Iwata H

• KMID: 2532786
• DOI: http://doi.org/10.4048/jbc.2022.25.e34

Abstract

Purpose
Safely postponing the use of chemotherapy is important for quality of life maintenance in patients with hormone receptor-positive advanced breast cancer. In previous studies, a combination of cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) and fulvestrant prolonged the time to chemotherapy (TTC). In this study, we used real-world data to evaluate TTC in the context of CDK4/6i therapy.
Methods
We performed a retrospective chart review of women with estrogen receptorpositive, human epidermal growth factor receptor 2-negative advanced breast cancer treated at the Aichi Cancer Center Hospital. The patients were categorized into having received CDK4/6i therapy first (n = 41), second (n = 33), and none at all (n = 67). The change in TTC among the groups was examined.
Results
The median follow-up time was 13.8, 27.5, and 30.3 months in the CDK4/6i (first), CDK4/6i (second), and non-CDK4/6i groups, respectively. The median progression-free survival (PFS) with first-line therapy for metastasis was 30.0, 11.9, and 13.0 months, respectively (CDK4/6i [first] vs. non-CDK4/6i; p = 0.018, CDK4/6i [second] vs. non-CDK4/6i; p = 0.383). The median TTC was not reached in the CDK4/6i (first) group, was 39.1 months in the CDK4/6i (second) group, and was 44.2 months in the non-CDK4/6i group (CDK4/6i [first] vs. non-CDK4/6i; p = 0.880; CDK4/6i [second] vs. non-CDK4/6i; p = 0.407). The nonCDK4/6i group with TTC ≥ 60 months included more cases of secondary endocrine therapy resistance (p = 0.017), no perioperative chemotherapy (p = 0.021), and a longer disease-free interval (p = 0.093).
Conclusion
Although PFS was significantly longer in the CDK4/6i (first) group than in the non-CDK4/6i group, TTC did not significantly differ among the three groups in real-world data. The non-CDK4/6i group showed a long TTC in patients with late recurrence and low risk at the primary lesion site, who benefited greatly from hormone monotherapy.

Keyword

Breast Neoplasms; Cyclin-Dependent Kinases; Neoplasm Metastasis; Receptors; Estrogen