近日，复旦大学附属肿瘤医院邵志敏团队研究了辅助卡铂强化化疗与标准化疗对高危、早期、三阴性癌症（CITRINE）患者生存率的影响。相关论文于2025年12月23日发表在《英国医学杂志》上。

为了评价表柔比星和环磷酰胺联合每周紫杉醇加或不加卡铂辅助治疗高危、早期三阴性乳腺癌的疗效和安全性，研究组进行了一项随机、开放标签、3期试验。2020年3月至2022年3月，在中国复旦大学上海癌症中心招募明确手术后可手术的高危三阴性乳腺癌女性患者（定义为区域淋巴结阳性或淋巴结阴性且Ki-67标记指数≥50%）。患者以1:1的比例随机分为卡铂组（四个周期，每周一次表阿霉素和环磷酰胺，然后是四个周期的紫杉醇与卡铂联合治疗）或对照组（四周，每周三次或每两周表阿霉素和化疗，然后是四周的紫杉醇治疗）。主要终点是意向治疗人群的无病生存期。次要终点包括无复发生存期、远端无疾病生存期、总生存期和安全性。

在808名入组患者中，807名接受了研究治疗。在中位随访44.7个月时，卡铂组3年无病患者的估计百分比为92.3%，对照组为85.8%(风险比0.64,95%可信区间（CI） 0.43至0.95；P = 0.03)。然而，对比例风险假设的评估显示其不符合（P=0.02）。分段风险模型显示，风险比随时间变化：0-12个月的风险比为0.31 (95% CI 0.13 ~ 0.73)， 12-36个月的风险比为0.65(0.39 ~ 1.09)，36个月的风险比为1.98（0.69 ~ 5.69）。对于次要终点，卡铂组在3年无复发生存率（93.8% v 88.3%；风险比0.59,95% CI 0.37至0.93；P=0.02）、3年远端无疾病生存率（94.8% v 89.8%；风险比0.61,0.37至0.98；P=0.04）和3年总生存率（98.0% v 94.0%；风险比0.41,0.20至0.83；P=0.01）方面均有改善。卡铂组3-4级治疗相关不良事件发生率为66.7%（403例患者中269例），对照组为55.0%（404例患者中222例）。无治疗相关死亡发生。

研究结果表明，卡铂在蒽环类/紫杉烷类辅助化疗的基础上显著改善了高风险、早期三阴性乳腺癌患者的生存结果，降低了早期复发风险，没有新的安全性问题。

附：英文原文

Title: Effect of adjuvant carboplatin intensified chemotherapy versus standard chemotherapy on survival in women with high risk, early stage, triple negative breast cancer (CITRINE): randomised, open label phase 3 trial

Author: Yin Liu, Yue Gong, Xiu-Zhi Zhu, Guang-Yu Liu, Ke-Da Yu, Fan Yang, Li Chen, Min He, Zhen Hu, Can-Ming Chen, A-Yong Cao, Jun-Jie Li, Yi-Feng Hou, Gen-Hong Di, Jiong Wu, Yi-Zhou Jiang, Lei Fan, Zhong-Hua Wang, Zhi-Ming Shao

Issue&Volume: 2025/12/23

Abstract:

Objective To evaluate the efficacy and safety of epirubicin and cyclophosphamide followed by weekly paclitaxel with or without carboplatin as adjuvant therapy for patients with high risk, early stage, triple negative breast cancer.

Design Randomised, open label, phase 3 trial.

Setting Fudan University Shanghai Cancer Center in China between March 2020 and March 2022.

Participants Female patients with operable high risk triple negative breast cancer (defined as either regional node positive or node negative with a Ki-67 labelling index of ≥50%) after definitive surgery.

Interventions Patients were randomised in a 1:1 ratio into either the carboplatin arm (four cycles of two weekly epirubicin and cyclophosphamide followed by four cycles of weekly paclitaxel combined with carboplatin) or the control arm (four cycles of three weekly or two weekly epirubicin and cyclophosphamide followed by four cycles of weekly paclitaxel).

Main outcome measures The primary endpoint was disease-free survival in the intention-to-treat population. Secondary endpoints included recurrence-free survival, distant disease-free survival, overall survival, and safety.

Results Of the 808 enrolled patients, 807 received study treatment. At a median follow-up of 44.7 months, estimated percentages of patients who would be disease-free at three years were 92.3% in the carboplatin arm and 85.8% in the control arm (hazard ratio 0.64, 95% confidence interval (CI) 0.43 to 0.95; P=0.03). However, the assessment of the proportional hazards assumption showed that it was violated (P=0.02). A piecewise hazard model showed that the hazard ratio changed over time: the hazard ratio was 0.31 (95% CI 0.13 to 0.73) for 0-12 months, 0.65 (0.39 to 1.09) for 12-36 months, and 1.98 (0.69 to 5.69) for >36 months. For secondary endpoints, the carboplatin arm was associated with improved outcomes in three year recurrence-free survival (93.8% v 88.3%; hazard ratio 0.59, 95% CI 0.37 to 0.93; P=0.02), three year distant disease-free survival (94.8% v 89.8%; hazard ratio 0.61, 0.37 to 0.98; P=0.04), and three year overall survival (98.0% v 94.0%; hazard ratio 0.41, 0.20 to 0.83; P=0.01). The incidence of grade 3-4 treatment related adverse events was 66.7% (269 of 403 patients) in the carboplatin arm and 55.0% (222 of 404 patients) in the control arm. No treatment related deaths occurred.

Conclusions The addition of carboplatin to adjuvant anthracycline/taxane based chemotherapy significantly improved survival outcomes in patients with high risk, early stage, triple negative breast cancer, driven by reduction of early recurrence risk without new safety concerns.

DOI: 10.1136/bmj-2025-085457

Source: https://www.bmj.com/content/391/bmj-2025-085457