中山大学附属肿瘤医院袁中玉团队研究了低剂量高频率卡培他滨维持治疗对接受标准治疗的早期三阴性乳腺癌患者无病生存率的影响。2020年12月10日，该研究发表在《美国医学会杂志》上。

在所有乳腺癌亚型中，三阴性乳腺癌在标准治疗后复发率较高且预后较差。因此需要有效的策略来减少复发和死亡的风险。

为了评价早期三阴性乳腺癌标准辅助化疗后低剂量卡培他滨维持治疗的疗效和不良反应，2010年4月至2016年12月，研究组在中国13个学术中心和临床机构进行了一项随机临床试验，随访的最后日期是2020年4月30日。

研究组共招募了443名患有早期三阴性乳腺癌的患者，均已完成标准辅助化疗。将其按1：1随机分配，其中222例以650 mg/m²的剂量每天两次口服卡培他滨，持续1年不间断；221例在完成标准辅助化疗后进行观察。主要终点是无病生存期。

443名参与者中有434名女性参与了全部分析，平均年龄为46岁，T1/T2分期占93.1％，淋巴结阴性占61.8％，共有98.0％完成了试验。中位随访61个月后，研究组共观察到94例事件，其中卡培他滨组中有38例，包括37例复发和32例死亡；观察组中有56例，包括56例复发和40例死亡。

卡培他滨组的估计5年无病生存率为82.8％，显著高于观察组（73.0％），复发或死亡的风险比为0.64。卡培他滨组与观察组中估计5年无远端转移生存率分别为85.8％与75.8％，差异显著；估计5年总生存率分别为85.5％和81.3％，估计5年局部无复发生存率分别为85.0％与80.8％，差异均不显著。与卡培他滨相关的最常见不良事件是手足综合征（45.2％），其中7.7％的患者经历了3级事件。

研究结果表明，对于接受标准辅助治疗的早期三阴性乳腺癌女性患者，采用低剂量卡培他滨维持治疗1年，与定期观察相比，可显著提高5年无病生存率。

附：英文原文

Title: Effect of Capecitabine Maintenance Therapy Using Lower Dosage and Higher Frequency vs Observation on Disease-Free Survival Among Patients With Early-Stage Triple-Negative Breast Cancer Who Had Received Standard Treatment: The SYSUCC-001 Randomized Clinical Trial

Author: Xi Wang, Shu-Sen Wang, Heng Huang, Li Cai, Li Zhao, Rou-Jun Peng, Ying Lin, Jun Tang, Jian Zeng, Le-Hong Zhang, Yong-Li Ke, Xian-Ming Wang, Xin-Mei Liu, Qian-Jun Chen, An-Qin Zhang, Fei Xu, Xi-Wen Bi, Jia-Jia Huang, Ji-Bin Li, Dan-Mei Pang, Cong Xue, Yan-Xia Shi, Zhen-Yu He, Huan-Xin Lin, Xin An, Wen Xia, Ye Cao, Ying Guo, Yan-Hong Su, Xin Hua, Xin-Yue Wang, Ruo-Xi Hong, Kui-Kui Jiang, Chen-Ge Song, Zhang-Zan Huang, Wei Shi, Yong-Yi Zhong, Zhong-Yu Yuan, South China Breast Cancer Group (SCBCG)

Issue&Volume: 2020-12-10

Abstract:

Importance  Among all subtypes of breast cancer, triple-negative breast cancer has a relatively high relapse rate and poor outcome after standard treatment. Effective strategies to reduce the risk of relapse and death are needed.

Objective  To evaluate the efficacy and adverse effects of low-dose capecitabine maintenance after standard adjuvant chemotherapy in early-stage triple-negative breast cancer.

Design, Setting, and Participants  Randomized clinical trial conducted at 13 academic centers and clinical sites in China from April 2010 to December 2016 and final date of follow-up was April 30, 2020. Patients (n=443) had early-stage triple-negative breast cancer and had completed standard adjuvant chemotherapy.

Interventions  Eligible patients were randomized 1:1 to receive capecitabine (n=222) at a dose of 650 mg/m2 twice a day by mouth for 1 year without interruption or to observation (n=221) after completion of standard adjuvant chemotherapy.

Main Outcomes and Measures  The primary end point was disease-free survival. Secondary end points included distant disease-free survival, overall survival, locoregional recurrence-free survival, and adverse events.

Results  Among 443 women who were randomized, 434 were included in the full analysis set (mean [SD] age, 46 [9.9] years; T1/T2 stage, 93.1%; node-negative, 61.8%) (98.0% completed the trial). After a median follow-up of 61 months (interquartile range, 44-82), 94 events were observed, including 38 events (37 recurrences and 32 deaths) in the capecitabine group and 56 events (56 recurrences and 40 deaths) in the observation group. The estimated 5-year disease-free survival was 82.8% in the capecitabine group and 73.0% in the observation group (hazard ratio [HR] for risk of recurrence or death, 0.64 [95% CI, 0.42-0.95]; P=.03). In the capecitabine group vs the observation group, the estimated 5-year distant disease-free survival was 85.8% vs 75.8% (HR for risk of distant metastasis or death, 0.60 [95% CI, 0.38-0.92]; P=.02), the estimated 5-year overall survival was 85.5% vs 81.3% (HR for risk of death, 0.75 [95% CI, 0.47-1.19]; P=.22), and the estimated 5-year locoregional recurrence-free survival was 85.0% vs 80.8% (HR for risk of locoregional recurrence or death, 0.72 [95% CI, 0.46-1.13]; P=.15). The most common capecitabine-related adverse event was hand-foot syndrome (45.2%), with 7.7% of patients experiencing a grade 3 event.

Conclusions and Relevance  Among women with early-stage triple-negative breast cancer who received standard adjuvant treatment, low-dose capecitabine maintenance therapy for 1 year, compared with observation, resulted in significantly improved 5-year disease-free survival.

DOI: 10.1001/jama.2020.23370

Source: https://jamanetwork.com/journals/jama/fullarticle/2774295