Tan Yujing, Peng Zexi, Jiang Hanfang, Ma Fei, Wang Jiayu, Zhang Pin, Li Qing, Tian Xinzhu, Han Yuhang, Ji Danyang, Xu Binghe, Zhao Weihong, Fan Ying
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.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Breast Oncology, Peking University Cancer Hospital and Institute, Beijing, China.
Ther Adv Med Oncol. 2024 Nov 16;16:17588359241292256. doi: 10.1177/17588359241292256. eCollection 2024.
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.
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.
This was a retrospective and multicenter study.
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.
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 for 13.5 months, PFS for 6.1 months, and PFS for 4.1 months ( = 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 ( = 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, = 3.6e-11, HR = 3.78, 95% CI = 2.49-5.74) and external validation cohort (PFS 13.5 vs 3.1 months, = 2.9e-10, HR = 11.53, 95% CI = 4.68-28.37) confirmed its power for estimating clinical benefits of everolimus.
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.
依维莫司对激素受体阳性且人表皮生长因子受体2阴性（HR+/HER2-）的晚期乳腺癌（ABC）患者有益。然而，一些患者出现了耐药性，且用于评估依维莫司疗效的成熟预测指标有限。
本研究旨在评估依维莫司在不同治疗线中的疗效，并确定几种临床病理标志物以评估HR+/HER2- ABC患者中依维莫司的疗效。
这是一项回顾性多中心研究。
2014年至2022年期间，从中国多个癌症中心（国家癌症中心、中国人民解放军总医院、北京大学肿瘤医院暨研究所）收集了2000多名接受依维莫司治疗的肿瘤患者。构建了一个训练队列和两个验证队列。
训练队列包括338例患者。依维莫司治疗的中位无进展生存期（PFS）为5.6个月，客观缓解率为25.1%，临床获益率为54.4%。从一线（1L）到二线（2L）再到三线（3L），PFS显著变差，1L的PFS为13.5个月，2L的PFS为6.1个月，3L的PFS为4.1个月（P = 2.9e - 6，风险比（HR）= 0.70，95%置信区间（CI）= 0.61 - 0.82）。临床病理特征，包括1L后依维莫司治疗、Ki67指数大于40%、首次复发时转移部位超过两个以及接受辅助化疗，是PFS的独立危险因素。使用这四个因素建立了依维莫司疗效的预测模型。在低风险组中，患者的中位PFS为12.6个月，与高风险组的2.7个月相比显著更长（P = 2.4e - 64，HR = 9.41，95% CI = 7.05 - 12.56）。6个月、1年和3年PFS的曲线下面积分别为0.96、0.95和0.94。内部验证队列（PFS 18.4 vs 3.1个月，P = 3.6e - 11，HR = 3.78，95% CI = 2.49 - 5.74）和外部验证队列（PFS 13.5 vs 3.1个月，P = 2.9e - 10，HR = 11.53，95% CI = 4.68 - 28.37）证实了其评估依维莫司临床获益的能力。
成功建立了一个预测模型，用于预测HR+/HER2- ABC患者中依维莫司的生存结局，这可能为中国HR+/HER2- ABC患者的依维莫司治疗管理提供参考。
