Real-world effectiveness of CDK4/6 inhibitors on patients with HR+/HER2– advanced breast cancer in South Korea, focusing on underrepresented patients

Abstract

Objective

We assessed the real-world effectiveness of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors as first-line treatments in postmenopausal patients with HR+/HER2− advanced breast cancer, focusing on younger (<45 years) and older (>78 years) populations not considered in clinical trials.

Methods

We analyzed nationwide claims data from the Health Insurance Review and Assessment Service between November 2016 and February 2021. In this retrospective cohort study, patients using CDK4/6 inhibitors and aromatase inhibitors were selected and grouped by age as follows: 45–78 years (trial-enrolled), <45 years (younger), and >78 years (older). We estimated the median real-world progression-free survival (rwPFS) and overall survival (OS) using the Kaplan-Meier method. We conducted Cox regression analysis using a sub-distribution hazard model to evaluate risk factors (age, history of prior systemic treatment, presence of metastasis, comorbidity index, and type of provider) and estimated hazard ratios (HR).

Results

Among the 2,830 patients who received CDK4/6 inhibitors as first-line therapy, we identified 358 (12.65%) younger and 148 (5.23%) older underrepresented patients. The younger patient group (50.84%) had the highest rate of prior systemic therapy, followed by the trial-enrolled (25.39%) and older patient groups (8.11%). The median rwPFS was shorter in the older group (19.30 months) than those in the younger and the trial-enrolled age groups (30.33 and 34.53 months, respectively; p = .002). The HR of older age for death was 1.59 (95% confidence interval (CI) = 1.24–2.03). For rwPFS, the HR of prior systemic therapy was 1.19 (95% CI = 1.04–1.37).

Conclusions

The younger age group, which was underrepresented in the trial, did not show a significant difference in risk compared with the enrolled age group. However, the older age group, which was also underrepresented in the trial, faces a risk of mortality but not progression. Patients who fall outside the specified age groups for the clinical trial can still expect the same level of effectiveness in terms of progression.

Keywords:

• Breast neoplasms
• cyclin-dependent kinase 4/6 inhibitor
• progression
• overall survival
• real-world study

Transparency

Declaration of funding

The authors declare no funding.

Declaration of financial/other relationships

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Hye-In Jung: Conception and design, data analysis and interpretation, and manuscript writing. Sun-Hong Kwon: Conception and design, data interpretation, and manuscript writing. Jin Hyun Nam: Data analysis and interpretation, and manuscript writing. Jeong-Yeon Cho: Data interpretation. Eui-Kyung Lee: Conception and design, provision of study materials, manuscript writing, and final approval of the manuscript.

Acknowledgements

This research was supported by the SungKyunKwan University and the BK21 FOUR (Graduate School Innovation) funded by the Ministry of Education (MOE, Korea) and National Research Foundation of Korea (NRF).

Data availability statement

This study used nationwide claims data from the Health Insurance Review and Assessment Service (HIRA research data M20210402202). The data may be shared with HIRA with permission.