Peng Xuenan, Lan Bo, Wang Jiayu, Li Qiao, Wang Jiani, Fan Ying, Luo Yang, Chen Shanshan, Mo Hongnan, Li Lixi, Sun Xiaoying, Zhang Jintao, Cai Ruigang, Zhang Pin, Xu Binghe, Ma Fei
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.
Department of Medical Oncology, Cancer Hospital of HuanXing ChaoYang District, Beijing, 100164, China.
Breast. 2025 Jun;81:104470. doi: 10.1016/j.breast.2025.104470. Epub 2025 Apr 4.
A growing number of antibody‒drug conjugates (ADCs) have been approved for breast cancer treatment. However, the proper sequential strategies of ADCs remain uncertain. Our study aimed to explore the ideal ADC sequential treatment strategies in human epidermal growth factor receptor 2 (HER2)-expressing metastatic breast cancer (MBC).
Our multi-centre retrospective study enrolled MBC patients who received at least 2 lines of different types of ADCs between Jan 1, 2018, and Jul 1, 2024. The efficacy of both ADC1 and ADC2 was evaluated.
A total of 111 patients (83 HER2-positive and 28 HER2-low) were included. In HER2-positive populations, Patients who received ADC2 with a different payload from ADC1 exhibited significantly longer progression-free survival 2 (PFS2) (6.8 vs. 2.7 months, p < 0.001) and overall PFS (progression-free Interval 1 (PFI1) + PFS2) (15.0 vs. 8.5 months, p = 0.043) compared to those treated with ADC2 containing a similar payload with ADC1. Patients received ADC2 immediately after ADC1 progression showed longer PFS2 ADC2 delayed sequential patients (median PFS2: 6.0 vs. 3.0 months, p = 0.004). In HER2-low patients, the efficacy of ADC2 tended to be lower than ADC1 (median PFI1 vs. PFS2: 3.1 vs. 2.4 months, p = 0.078). No significant differences of efficacy were observed, no matter what ADC sequential treatment strategy used.
Sequential treatment with ADCs showed clinical benefit especially for HER2-positive patients treated with ADC2 which have different types of payloads from ADC1. In HER2-low patients, the benefit of ADC sequential therapy seemed to be limited.
越来越多的抗体药物偶联物（ADC）已被批准用于乳腺癌治疗。然而，ADC的合理序贯策略仍不明确。我们的研究旨在探索在人表皮生长因子受体2（HER2）表达的转移性乳腺癌（MBC）中理想的ADC序贯治疗策略。
我们的多中心回顾性研究纳入了在2018年1月1日至2024年7月1日期间接受至少2线不同类型ADC治疗的MBC患者。评估了ADC1和ADC2的疗效。
共纳入111例患者（83例HER2阳性和28例HER2低表达）。在HER2阳性人群中，与接受含与ADC1相似有效载荷的ADC2治疗的患者相比，接受与ADC1有效载荷不同的ADC2治疗的患者表现出显著更长的无进展生存期2（PFS2）（6.8个月对2.7个月，p<0.001）和总无进展生存期（无进展间期1（PFI1）+PFS2）（15.0个月对8.5个月，p=0.043）。ADC1进展后立即接受ADC2治疗的患者显示出比ADC2延迟序贯治疗的患者更长的PFS2（中位PFS2：6.0个月对3.0个月，p=0.004）。在HER2低表达患者中，ADC2的疗效倾向于低于ADC1（中位PFI1对PFS2：3.1个月对2.4个月，p=0.078）。无论采用何种ADC序贯治疗策略，均未观察到疗效的显著差异。
ADC序贯治疗显示出临床益处，特别是对于接受与ADC1有效载荷类型不同的ADC2治疗的HER2阳性患者。在HER2低表达患者中，ADC序贯治疗的益处似乎有限。
