Suo Jiaojiao, Zhu Kunrui, Zhuang Chunying, Zhong Xiaorong, Bravaccini Sara, Maltoni Roberta, Bertucci François, Zheng Hong, Luo Ting
Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Breast Center, West China Hospital, Sichuan University, Chengdu, China.
Ann Transl Med. 2023 Dec 20;11(12):409. doi: 10.21037/atm-23-1913. Epub 2023 Dec 19.
Tucidinostat, which is a subtype-selective histone deacetylase inhibitor, has been approved in China for the treatment of hormone receptor-positive (HR) human epidermal growth factor receptor 2-negative (HER2) advanced breast cancer (ABC). However, existing evidence mainly stemmed from randomized controlled trials, and might have limitations in representing the complexities of clinical practice and diverse patient populations. Therefore, there is a need to explore the efficacy and optimal therapeutic modality for tucidinostat in real-world clinical settings.
The objective of this real-world study was to analyze the clinical data of 47 patients with HR/HER2 ABC who received tucidinostat treatment at West China Hospital, Sichuan University, between August 2020 and May 2023. The primary outcomes were progression-free survival (PFS) and clinical benefit rate [CBR; defined as partial response (PR) and stable disease (SD) for ≥6 months on clinical evaluation].
A total of 47 patients were included, and the median follow-up time was 18.20 months. The median line of tucidinostat therapy was 3 (range, 1-9). In all, 52.17% patients were treated with tucidinostat plus fulvestrant, while 38.30% were treated with tucidinostat plus aromatase inhibitors. Notably, 10.64% of the patients with rapidly progressing visceral metastases received tucidinostat plus endocrine therapy as maintenance treatment after achieving disease control with chemotherapy. The median PFS was 4.43 months [95% confidence interval (CI), 2.77-10.53], and the median overall survival was 19.57 months (95% CI, 12.83-not reached). The 6-month CBR for the overall population was 41.86%. Patients undergoing maintenance therapy demonstrated a significantly longer PFS than did those who did not receive it as maintenance therapy (14.13 . 3.93 months; P=0.01). Univariate Cox regression analysis showed that use of tucidinostat in lines 1-2, use of tucidinostat plus fulvestrant, presence of one metastatic site, and lack of brain metastasis were favorable factors for PFS. Thrombocytopenia was the most frequently reported adverse event, with an incidence rate of 31.91% at all grades and 14.89% at grade ≥3. Four (8.51%) patients discontinued the treatment.
For patients with HR/HER2 ABC, tucidinostat combination therapy offers certain survival benefits with controllable safety. Furthermore, compared with non-maintenance therapy, maintenance therapy after chemotherapy may have promising efficacy.
图西诺司他是一种亚型选择性组蛋白去乙酰化酶抑制剂，已在中国获批用于治疗激素受体阳性（HR）、人表皮生长因子受体2阴性（HER2）的晚期乳腺癌（ABC）。然而，现有证据主要来自随机对照试验，在反映临床实践的复杂性和不同患者群体方面可能存在局限性。因此，有必要在真实世界的临床环境中探索图西诺司他的疗效和最佳治疗方式。
这项真实世界研究的目的是分析2020年8月至2023年5月期间在四川大学华西医院接受图西诺司他治疗的47例HR/HER2 ABC患者的临床数据。主要结局指标为无进展生存期（PFS）和临床获益率[CBR；定义为临床评估中部分缓解（PR）和疾病稳定（SD）≥6个月]。
共纳入47例患者，中位随访时间为18.20个月。图西诺司他治疗的中位线数为3（范围1 - 9）。总体而言，52.17%的患者接受图西诺司他联合氟维司群治疗，而38.30%的患者接受图西诺司他联合芳香化酶抑制剂治疗。值得注意的是，10.64%内脏转移快速进展的患者在化疗实现疾病控制后接受图西诺司他联合内分泌治疗作为维持治疗。中位PFS为4.43个月[95%置信区间（CI），2.77 - 10.53]，中位总生存期为19.57个月（95% CI，12.83 - 未达到）。总体人群的6个月CBR为41.86%。接受维持治疗的患者的PFS明显长于未接受维持治疗的患者（14.13对3.93个月；P = 0.01）。单因素Cox回归分析显示，一线至二线使用图西诺司他、使用图西诺司他联合氟维司群、存在一个转移部位以及无脑转移是PFS的有利因素。血小板减少症是报告最频繁的不良事件，所有级别发生率为31.91%，≥3级发生率为14.89%。4例（8.51%）患者停止治疗。
对于HR/HER2 ABC患者，图西诺司他联合治疗可提供一定的生存获益且安全性可控。此外，与非维持治疗相比，化疗后维持治疗可能具有良好疗效。
