Beyond clinical trials: CDK4/6 inhibitor efficacy predictors and nomogram model from real-world evidence in metastatic breast cancer

Binliang Liu; Zhe-Yu Hu; Ning Xie; Liping Liu; Jing Li; Xiaohong Yang; Huawu Xiao; Xuran Zhao; Can Tian; Hui Wu; Jun Lu; Jianxiang Gao; Xuming Hu; Min Cao; Zhengrong Shui; Yu Tang; Quchang Ouyang

doi:10.1002/cai2.143

Beyond clinical trials: CDK4/6 inhibitor efficacy predictors and nomogram model from real-world evidence in metastatic breast cancer

Cancer Innov. 2024 Oct 25;3(6):e143. doi: 10.1002/cai2.143. eCollection 2024 Dec.

Authors

Binliang Liu¹, Zhe-Yu Hu¹, Ning Xie¹, Liping Liu¹, Jing Li¹, Xiaohong Yang¹, Huawu Xiao¹, Xuran Zhao², Can Tian¹, Hui Wu¹, Jun Lu¹, Jianxiang Gao¹, Xuming Hu¹, Min Cao¹, Zhengrong Shui¹, Yu Tang³, Quchang Ouyang¹

Affiliations

¹ Department of Breast Cancer Medical Oncology Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University Changsha Hunan China.
² Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China.
³ Department of Gastroenterology The Third Xiangya Hospital of Central South University Changsha Hunan China.

Abstract

Background: CDK4/6 inhibitors (CDK4/6i) have shown promising results in the treatment of hormone receptor-positive (HR+) metastatic breast cancer (MBC) when combined with endocrine therapy (ET). It is crucial to evaluate the actual effectiveness and safety of CDK4/6i in clinical practice, as well as to analyze the factors that can predict their outcomes.

Methods: Patients with HR+ MBC who received CDK4/6i-based therapy between May 2016 and May 2023 at Hunan Cancer Hospital were evaluated for progression-free survival (PFS). Adverse reactions were assessed based on the National Cancer Institute Common Toxicity Criteria (version 5.0).

Results: This study included 344 patients, with a median PFS (mPFS) of 12.8 months (range: 10.4-15.2 months). After adjustment, Cox multivariate regression analysis revealed that visceral metastasis (specifically liver and brain metastases), Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥ 1, estrogen receptor ≤ 80%, progesterone receptor ≤ 10%, Ki-67 > 30%, and treatment in later stages were significant factors associated with reduced PFS. Based on this, we created a prognostic nomogram and validated its performance, obtaining a C-index of 0.714 (95% confidence interval: 0.640-0.787) as well as reliable calibration and clinical impact. The mPFS of CDK4/6i rechallenge was 7.7 months; for patients who initially discontinued CDK4/6i for reasons other than disease progression, CDK4/6i rechallenge still provided a mPFS of 11.4 months. The tolerability and safety of combining CDK4/6is with ET were manageable. Adverse events led to treatment discontinuation in 3.8% of patients. Neutropenia (29.1%), leukopenia (13.7%), and anemia (4.1%) were the primary grade 3/4 adverse reactions.

Conclusions: This real-world study highlights the ample efficacy and reasonable safety of combined CDK4/6i and ET in patients with HR+ MBC. Individualized treatment decisions and ongoing safety monitoring are important to optimize the therapeutic benefit of CDK4/6i treatment.

Keywords: CDK4/6 inhibitor; breast cancer; efficacy; predictive factors; real‐word study.