诺拉替尼治疗表皮生长因子-2过表达难治性转移性乳腺癌的临床实践

Clinical Experience of Neratinib in the Treatment of HER-2 Overexpressed Refractory Metastatic Breast Cancer

目的研究单药诺拉替尼(neratinib)和诺拉替尼联合曲妥珠单抗治疗表皮生长因子受体-2(HER-2)过表达难治性复发转移性乳腺癌的疗效和安全性。方法 17例HER-2过表达难治性复发转移性乳腺癌,其中10例为既往曲妥珠单抗治疗失败患者,4例为无症状脑转移患者。9例接受单药诺拉替尼治疗,8例接受诺拉替尼联合曲妥珠单抗治疗。诺拉替尼为口服240mg.d-1;曲妥珠单抗为首剂4 mg.kg-1静滴,维持剂量为2 mg.kg-1.周-1静滴。每4周为1周期,每2周期评价疗效同时记录不良事件。结果 17例患者可评价疗效,1例完全缓解,部分缓解8例,有效率52.9%(9/17)。单药诺拉替尼组有效率77.7%(7/9),诺拉替尼联合曲妥珠单抗组有效率25%(2/8)。2例脑转移患者颅内病灶明显好转,2例脑转移颅内病灶稳定。共17例患者261周期可评价毒性反应,其中腹泻是主要不良反应,Ⅱ～Ⅲ度占47.1%(8/17),预防性应用止泻药物后可以得到控制。结论单药诺拉替尼和诺拉替尼联合曲妥珠单抗是治疗HER-2过表达难治性复发转移性乳腺癌的有效方案,部分脑转移患者中显示出一定疗效。其最常见不良反应为腹泻,经过对症处理后总体不良反应能够耐受。

OBJECTIVE To study the efficacy and safety of neratinib monotherapy and neratinib/trastuzumab combination therapy in the treatment of human epidermal growth factor receptor 2 （HER-2） overexpressed refractory metastatic breast cancer. METHODS Among 17 patients with HER-2 overexpressed refractory metastatic breast cancer, 9 were previous trastuzumab treatment failure patients, 4 were asymptomatie patients with brain metastases. Nine patients received neratinib monotberapy, and 8 patients received neratinib/trastuzumab combination therapy. Neratinib was taken orally 240 mg.d- 1; trastuzumab was intravenously injected at a loading dose of 4 mg . kg-1 and maintenance dose of 2 mg.kg-1 intravenously once a week. Four weeks were a treatment cycle. The effi- cacy was evaluated every 2 weeks, at the same time adverse events were also recorded. RESULTS All 17 patients were evaluated. One had complete response, and 8 cases showed partial response. Therefore, the response （CR ＋ PR） rate was 52. 9% （9/17.）. The response rates were 77.7% （7/9） and 25% （2/8） for neratinib monotherapy, and neratinib/trastuzumab combination group, respectively. The intraeranial lesions in 2 patients with brain metastases got significantly improved, and the other 2 eases were stable. Totally 17 patients were evaluable for toxicity for 261 cycles. Diarrhea was the main adverse reaction, of which Ⅱ- Ⅲ degree occupied 47. 1% （8/17） , but it could be controlled by prophylactic use of antidiarrheal drugs. CONCLUSION Neratinib monotherapy and neratinib/trastuzumab combination therapy are effective and safe in the treatment of HER-2 overexpressed refractory metastatic breast cancer. Some patients with brain metastases also have response to a certain extent. The most common adverse event is diarrhea. After symptomatic treatment, the overall adverse reactions can be tolerated.