Phase I Clinical Trial Center, Fudan University Shanghai Cancer Center, Shanghai, China.
Thorac Cancer. 2023 Dec;14(34):3381-3388. doi: 10.1111/1759-7714.15130. Epub 2023 Oct 20.
The clinical characteristics and efficacy of human epidermal growth factor receptor-2 (HER-2)-directed agents against HER2 mutations and HER2 fusions in breast cancer are obscure due to their low frequency.
We conducted a retrospective study in patients with advanced breast cancer harboring HER2 mutations and/or HER2 fusions between January 1, 2017 and January 1, 2021.
Among a total of 22 patients, 17 HER2 mutations were detected, including L755S, S310F, R100=, V777L, R897W, T862A, 440-17C > G, H878Y, V842I, 73 + 9G > C, T278fs, E1069K, L755P, 226-11C > T, 574 + 12C>T, L114V and P128L. The majority of patients had ductal carcinoma, which mostly coexisted with HER2 amplification/overexpression. The median progression-free survival (PFS) of the 22 patients was 6.9 months (95% CI: 4.7, 9.1) in the first-line setting. The median PFS of patients who received first-line trastuzumab-based regimens was significantly longer than that of patients who received a first-line tyrosine kinase inhibitor (TKI) (10.8 months [95% CI: 2.9, 18.7] vs. 1.9 months [95% CI: 0.8, 3.0], p < 0.005). A total of 14 patients were treated with anti-HER2 antibody-drug conjugate (ADC), among whom the median treatment line of first-time of administration of anti-HER2 ADC was 4.5 (range, 1-10). Anti-HER2 ADC reached an objective response rate (ORR) of 42.9%, a disease control rate (DCR) of 85.7% and a median PFS of 7.3 months (95% CI: 4.4-10.1) from the first-time of administration.
Our data demonstrated the clinical benefit of anti-HER2 treatment in Chinese breast cancer patients harboring HER2 mutation and/or HER2 fusion. The value of immunotherapy and treatment selection among individual HER2 variants needs further study.
由于 HER2 突变和/或 HER2 融合在乳腺癌中的频率较低，针对这些突变和融合的人表皮生长因子受体 2（HER-2）靶向药物的临床特征和疗效尚不明确。
我们对 2017 年 1 月 1 日至 2021 年 1 月 1 日期间患有 HER2 突变和/或 HER2 融合的晚期乳腺癌患者进行了回顾性研究。
在总共 22 名患者中，检测到 17 种 HER2 突变，包括 L755S、S310F、R100=、V777L、R897W、T862A、440-17C>G、H878Y、V842I、73+9G>C、T278fs、E1069K、L755P、226-11C>T、574+12C>T、L114V 和 P128L。大多数患者患有导管癌，大多数与 HER2 扩增/过表达并存。22 名患者的中位无进展生存期（PFS）在一线治疗中为 6.9 个月（95%CI：4.7，9.1）。接受曲妥珠单抗为基础的一线治疗方案的患者中位 PFS 明显长于接受一线酪氨酸激酶抑制剂（TKI）的患者（10.8 个月[95%CI：2.9，18.7]与 1.9 个月[95%CI：0.8，3.0]，p<0.005）。共有 14 名患者接受了抗 HER2 抗体药物偶联物（ADC）治疗，其中首次使用抗 HER2 ADC 的中位治疗线数为 4.5（范围 1-10）。从首次给药开始，抗 HER2 ADC 达到了 42.9%的客观缓解率（ORR）、85.7%的疾病控制率（DCR）和 7.3 个月的中位无进展生存期（95%CI：4.4-10.1）。
我们的数据表明，抗 HER2 治疗在中国乳腺癌患者中具有临床获益，这些患者携带有 HER2 突变和/或 HER2 融合。免疫治疗的价值和个体 HER2 变异体的治疗选择需要进一步研究。
