Everolimus treatment in patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer and a predictive model for its efficacy: a multicenter real-world study

Yujing Tan; Zexi Peng; Hanfang Jiang; Fei Ma; Jiayu Wang; Pin Zhang; Qing Li; Xinzhu Tian; Yuhang Han; Danyang Ji; Binghe Xu; Weihong Zhao; Ying Fan

doi:10.1177/17588359241292256

Everolimus treatment in patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer and a predictive model for its efficacy: a multicenter real-world study

Ther Adv Med Oncol. 2024 Nov 16:16:17588359241292256. doi: 10.1177/17588359241292256. eCollection 2024.

Authors

Yujing Tan¹, Zexi Peng¹, Hanfang Jiang², Fei Ma¹, Jiayu Wang¹, Pin Zhang¹, Qing Li¹, Xinzhu Tian¹, Yuhang Han¹, Danyang Ji¹, Binghe Xu¹, Weihong Zhao³, Ying Fan⁴

Affiliations

¹ Department of Medical Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
² Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Breast Oncology, Peking University Cancer Hospital and Institute, Beijing, China.
³ Department of Medical Oncology, Chinese PLA General Hospital, Beijing 100853, China.
⁴ Department of Medical Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

Abstract

Background: Everolimus is beneficial for patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). However, some patients developed drug resistance and the well-established predictor for everolimus efficacy was limited.

Objectives: The study was designed to evaluate the efficacy of everolimus in different treatment lines and identify several clinicopathological markers to estimate everolimus efficacy in patients with HR+/HER2- ABC.

Design: This was a retrospective and multicenter study.

Methods: Between 2014 and 2022, more than 2000 patients with tumors who received everolimus were collected from multiple cancer centers in China (National Cancer Center, Chinese PLA General Hospital, Peking University Cancer Hospital & Institute). A training cohort and two validation cohorts were developed.

Results: The training cohort included 338 patients. The median progression-free survival (PFS) for everolimus was 5.6 months, with an objective response rate of 25.1% and a clinical benefit rate of 54.4%. PFS was significantly worse from first-line (1L) to second-line (2L) to third-line (3L), with PFS_1L for 13.5 months, PFS_2L for 6.1 months, and PFS_3L for 4.1 months (p = 2.9e-6, hazard ratio (HR) = 0.70, 95% confidence interval (CI) = 0.61-0.82). The clinicopathological characteristics, including post-1L everolimus treatment, Ki67 index of more than 40%, more than two metastatic sites at first recurrence, and receiving adjuvant chemotherapy, were independent risk factors for PFS. A predictive model for everolimus efficacy was established using these four factors. In the low-risk group, patients achieved a median PFS of 12.6 months, significantly longer compared to 2.7 months for those in the high-risk group (p = 2.4e-64, HR = 9.41, 95% CI = 7.05-12.56). The area under the curve was 0.96, 0.95, and 0.94 for 6-month, 1-year, and 3-year PFS, respectively. Internal validation cohort (PFS 18.4 vs 3.1 months, p = 3.6e-11, HR = 3.78, 95% CI = 2.49-5.74) and external validation cohort (PFS 13.5 vs 3.1 months, p = 2.9e-10, HR = 11.53, 95% CI = 4.68-28.37) confirmed its power for estimating clinical benefits of everolimus.

Conclusion: A predictive model was successfully established to predict survival outcomes for everolimus in patients with HR+/HER2- ABC, which may provide references for the management of everolimus in Chinese patients with HR+/HER2- ABC.

Keywords: advanced breast cancer; efficacy; everolimus; predictive model; survival.