Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Clin Breast Cancer. 2011 Apr;11(2):103-13. doi: 10.1016/j.clbc.2011.03.003. Epub 2011 Apr 11.
Because chemotherapy for metastatic breast cancer (MBC) is associated with relevant toxicity, sequential monotherapy trastuzumab followed by cytotoxic therapy at disease progression might be an attractive approach.
In a multicenter phase II trial, 101 patients with overexpression of human epidermal growth factor receptor 2 (HER2(+)) MBC were randomized between combination-therapy trastuzumab (Herceptin) plus docetaxel (H+D) and sequential therapy of single-agent trastuzumab followed at disease progression by docetaxel alone (H→D) as first-line chemotherapy for metastatic disease. The primary endpoint was progression-free survival (PFS) after completed sequential or combination therapy.
For the H+D group the median PFS was 9.4 vs. 9.9 months for the H→D group and 1-year PFS rates were 44% vs. 35%, respectively. However the overall response rates (ORRs) were 79% vs. 53%, respectively (P = .016), and overall survival was 30.5 vs. 19.7 months, respectively (P = .11). In the H→D group, response rates to monotherapy trastuzumab and subsequent docetaxel were 34% and 39%, respectively, with a median PFS during single-agent trastuzumab of 3.9 months. The incidence and severity of neuropathy were significantly higher in the H+D group. Retrospective analysis of trastuzumab treatment beyond progression (applied in 46% of patients in the H+D group and 37% in the H→D group) showed a correlation with longer overall survival in both treatment arms (36.0 vs. 18.0 months and 30.3 vs. 18.6 months, respectively).
First-line treatment in patients with MBC with H→D resulted in a similar PFS compared with H+D, but the response rate was lower and the overall survival nonsignificantly shorter.
由于转移性乳腺癌（MBC）的化疗相关毒性，在疾病进展时序贯曲妥珠单抗单药治疗然后用细胞毒药物治疗可能是一种有吸引力的方法。
在一项多中心的 II 期临床试验中，101 例人表皮生长因子受体 2（HER2(+））MBC 患者被随机分为联合治疗组（曲妥珠单抗联合多西他赛，H+D）和序贯治疗组（先给予单药曲妥珠单抗，疾病进展时给予多西他赛，H→D），作为转移性疾病的一线化疗。主要终点是完成序贯或联合治疗后的无进展生存期（PFS）。
H+D 组的中位 PFS 为 9.4 个月，H→D 组为 9.9 个月，1 年 PFS 率分别为 44%和 35%。然而，总缓解率（ORR）分别为 79%和 53%（P =.016），总生存期分别为 30.5 个月和 19.7 个月（P =.11）。在 H→D 组，单药曲妥珠单抗和随后多西他赛的缓解率分别为 34%和 39%，单药曲妥珠单抗的中位 PFS 为 3.9 个月。H+D 组的周围神经病变发生率和严重程度显著较高。在 H+D 组中有 46%和 H→D 组中有 37%的患者在疾病进展后继续曲妥珠单抗治疗的回顾性分析显示，在两个治疗组中均与总生存期延长相关（分别为 36.0 个月和 18.0 个月，30.3 个月和 18.6 个月）。
在 MBC 患者中，H→D 一线治疗的 PFS 与 H+D 相似，但缓解率较低，总生存期无显著缩短。
