Okines Alicia, Irfan Tazia, Khabra Komel, Smith Ian, O'Brien Mary, Parton Marina, Noble Jill, Stanway Susie, Somaiah Navita, Ring Alistair, Johnston Stephen, Turner Nicholas
The Royal Marsden NHS Foundation Trust, London and Surrey, UK.
Breast J. 2018 May;24(3):253-259. doi: 10.1111/tbj.12906. Epub 2017 Aug 22.
Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that does not cross an intact blood-brain barrier. In the EMILIA trial of T-DM1 vs capecitabine/lapatinib for HER2 positive advanced breast cancer, all patients had baseline brain imaging, and 9/450 (2%) of patients with negative baseline imaging developed new brain disease during T-DM1. We assessed the frequency of brain progression in clinical practice, without routine baseline imaging. We undertook a retrospective study of all patients treated with T-DM1 at the Royal Marsden Hospital from 2011 to 2016. Data collected included baseline characteristics, previous treatment for advanced breast cancer, sites of metastatic disease, duration of T-DM1, sites of progression, and treatment of CNS progression. Fifty-five patients were identified who had received a median of two prior lines of treatment (range 0-5). All were HER2 positive; 45 patients had IHC 3+ tumors and 10 were ISH positive. Patients received a median of 12 cycles of T-DM1 (range 1-34), and six remain on treatment at the time of analysis. Before commencing T-DM1, 16/55 (29%) had known brain metastases (treated with whole brain [9] stereotactic radiotherapy [6] or both [1]). Brain was the first site of progression in 56% (9/16) patients, with a median time to brain progression of 9.9 months (95% CI 3.9-12.2). In patients without known baseline brain metastases, 17.9% (7/39) developed new symptomatic brain disease during T-DM1, after a median of 7.5 months (95%CI 3.8-9.6). Brain progression was isolated, with control of extra-cranial disease in 4/7 patients. Only one patient was suitable for stereotactic radiotherapy. Median time to extra-cranial progression in all patients was 11.5 months (95% CI 9.1-17.7), and median OS in all patients was 17.8 months (95% CI 14.2-22). In patients not screened for brain metastases at baseline, the brain was the first site of progression in a significant proportion. Baseline brain imaging may have a role in standard practice for patients commencing T-DM1 therapy.
ado曲妥珠单抗（T-DM1）是一种抗体药物偶联物，无法穿过完整的血脑屏障。在T-DM1与卡培他滨/拉帕替尼治疗HER2阳性晚期乳腺癌的EMILIA试验中，所有患者均进行了基线脑成像检查，在T-DM1治疗期间，450例基线成像阴性的患者中有9例（2%）出现了新的脑部疾病。我们评估了在临床实践中，无常规基线成像情况下脑转移进展的频率。我们对2011年至2016年在皇家马斯登医院接受T-DM1治疗的所有患者进行了一项回顾性研究。收集的数据包括基线特征、既往晚期乳腺癌治疗情况、转移病灶部位、T-DM1治疗持续时间、进展部位以及中枢神经系统进展的治疗情况。共确定了55例患者，他们接受的既往治疗中位数为2线（范围0-5线）。所有患者均为HER2阳性；45例患者肿瘤免疫组化（IHC）为3+，10例原位杂交（ISH）阳性。患者接受T-DM1治疗的中位数为12个周期（范围1-34个周期），分析时6例患者仍在接受治疗。在开始T-DM1治疗前，55例患者中有16例（29%）已知有脑转移（9例接受全脑放疗，6例接受立体定向放疗，1例两者均接受）。脑转移是9例（56%）患者的首个进展部位，脑转移进展的中位时间为9.9个月（95%置信区间3.9-12.2）。在基线时无已知脑转移的患者中，17.9%（7/39）在T-DM1治疗期间出现了新的有症状的脑部疾病，中位时间为7.5个月（95%置信区间3.8-9.6）。脑转移进展是孤立发生的，7例患者中有4例颅外疾病得到控制。只有1例患者适合立体定向放疗。所有患者颅外进展的中位时间为11.5个月（95%置信区间9.1-17.7），所有患者的中位总生存期为17.8个月（95%置信区间14.2-22）。在基线时未进行脑转移筛查的患者中，相当一部分患者脑转移是首个进展部位。基线脑成像检查可能在开始T-DM1治疗的患者的标准治疗中发挥作用。
