Murthy Rashmi K, Varma Ankur, Mishra Priyankana, Hess Kenneth R, Young Elliana, Murray James L, Koenig Kimberly H, Moulder Stacy L, Melhem-Bertrandt Amal, Giordano Sharon H, Booser Daniel, Valero Vicente, Hortobagyi Gabriel N, Esteva Francisco J
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Cancer. 2014 Jul 1;120(13):1932-8. doi: 10.1002/cncr.28689. Epub 2014 Mar 26.
The purpose of the current study was to describe the outcomes of patients with human epidermal growth factor receptor 2 (HER2)-overexpressed/amplified (HER2+) early breast cancer who received adjuvant or neoadjuvant trastuzumab-based therapy and were subsequently retreated with trastuzumab for metastatic disease.
A total of 353 patients with metastatic HER2+ breast cancer who were treated with trastuzumab as part of their first-line treatment for metastatic disease were identified. A total of 75 patients had received adjuvant or neoadjuvant trastuzumab-based therapy for early breast cancer, and 278 had not. Clinical outcomes of patients who had or had not received prior trastuzumab were compared using Cox proportional hazards regression and logistic regression analyses. Survival was estimated using the Kaplan-Meier method.
The clinical benefit (complete response, partial response, or stable disease of ≥ 6 months) rates were 71% in the group who did not receive prior trastuzumab and 39% in the group previously treated with trastuzumab. The adjusted odds ratios were 0.28 (95% confidence interval [95% CI], 0.13-0.59; P = .0009) for clinical benefit rates and 0.39 (95% CI, 0.18-0.82; P = .038) for objective (complete or partial) response rates. In the univariate analysis, the median overall survival rate was longer in the group who did not receive prior trastuzumab (36 months vs 28 months) (hazards ratio, 1.47; 95% CI, 1.07-2.01 [P = .022]). The multivariate analysis found no significant difference in overall survival.
When treated with trastuzumab for metastatic disease, patients with HER2+ breast cancer without prior exposure to trastuzumab were found to have superior clinical outcomes to those with prior exposure. Prior trastuzumab exposure should be considered in treatment algorithms and in HER2-targeted clinical trial enrollment for metastatic disease.
本研究旨在描述接受辅助或新辅助曲妥珠单抗治疗后，因转移性疾病再次接受曲妥珠单抗治疗的人表皮生长因子受体2（HER2）过表达/扩增（HER2+）早期乳腺癌患者的治疗结果。
共纳入353例接受曲妥珠单抗作为转移性疾病一线治疗一部分的转移性HER2+乳腺癌患者。其中75例患者曾接受早期乳腺癌的辅助或新辅助曲妥珠单抗治疗，278例未接受过。使用Cox比例风险回归和逻辑回归分析比较接受或未接受过曲妥珠单抗治疗的患者的临床结局。采用Kaplan-Meier法估计生存率。
未接受过曲妥珠单抗治疗的患者组临床获益（完全缓解、部分缓解或疾病稳定≥6个月）率为71%，先前接受过曲妥珠单抗治疗的患者组为39%。临床获益率的调整优势比为0.28（95%置信区间[95%CI]，0.13 - 0.59；P = 0.0009），客观（完全或部分）缓解率的调整优势比为0.39（95%CI，0.18 - 0.82；P = 0.038）。单因素分析中，未接受过曲妥珠单抗治疗的患者组中位总生存率更长（36个月对28个月）（风险比，1.47；95%CI，1.07 - 2.01[P = 0.022]）。多因素分析未发现总生存率有显著差异。
在接受曲妥珠单抗治疗转移性疾病时，未接触过曲妥珠单抗的HER2+乳腺癌患者的临床结局优于有过接触史的患者。在转移性疾病的治疗方案和HER2靶向临床试验入组中应考虑既往曲妥珠单抗接触史。
