Fan Yun, Chen Jianhua, Zhou Chengzhi, Wang Huijuan, Shu Yongqian, Zhang Jacky, Hua Hairui, Huang Dennis Chin-Lun, Zhou Caicun
Zhejiang Cancer Hospital, Hangzhou, China.
Hunan Cancer Hospital, Changsha, China.
Lung Cancer. 2020 Sep;147:209-213. doi: 10.1016/j.lungcan.2020.07.017. Epub 2020 Jul 16.
Despite 1-4 % of NSCLC tumors harboring mutations in the HER2 gene, there are no approved HER2-pathway-targeted treatments available. We report an open-label, single-arm, multicenter phase II study investigating the efficacy and safety of afatinib in Asian patients with HER2-mutation positive (HER2m+) NSCLC.
Eligible patients for Part A had confirmed stage IIIb/IV HER2m + NSCLC, had failed one or two prior lines of chemotherapy, and were EGFR/HER2-inhibitor naïve. Patients received oral afatinib 40 mg/day in continuous 28-day cycles, until disease progression or intolerable adverse events (AEs). Patients qualified for Part B if they had > 12 weeks' clinical benefit and Eastern Cooperative Oncology Group performance status ≤ 2. In Part B, patients were to receive afatinib at the last received dose, plus paclitaxel 80 mg/m weekly, until disease progression or intolerable AEs. The primary endpoint in Part A was objective response (OR); secondary endpoints included disease control (DC), progression-free survival (PFS), and overall survival (OS). Further exploratory endpoints were OR, DC, and PFS in Part B.
Eighteen patients received afatinib in Part A. No patient achieved an OR; 11 patients (61.1 %) achieved stable disease, and six patients (33.3 %) had progressive disease. DC rate was therefore 61.1 % (95 % confidence interval [CI]: 35.7, 82.7). A decrease in tumor size from baseline of > 0 to < 30 % was observed in eight patients. At the time of analysis, 16 patients (88.9 %) had progressed or died. Median PFS was 2.76 months (95 % CI: 1.87, 4.60) and median OS was 10.02 months (95 % CI: 8.47, 10.08). All patients experienced ≥ 1 AE, most commonly diarrhea (66.7 %) and rash (33.3 %). No patients met the inclusion criteria for Part B, and recruitment was slow; therefore, the study was terminated.
This study found no clinical benefit of afatinib for EGFR TKI-naïve patients with HER2m + NSCLC.
尽管1%-4%的非小细胞肺癌（NSCLC）肿瘤存在HER2基因突变，但目前尚无获批的针对HER2通路的靶向治疗药物。我们开展了一项开放标签、单臂、多中心II期研究，以调查阿法替尼在HER2突变阳性（HER2m+）的亚洲NSCLC患者中的疗效和安全性。
A部分的合格患者确诊为IIIb/IV期HER2m+ NSCLC，既往接受过一线或二线化疗且治疗失败，并且未曾使用过EGFR/HER2抑制剂。患者接受口服阿法替尼40 mg/天，每28天为一个连续周期，直至疾病进展或出现无法耐受的不良事件（AE）。如果患者有超过12周的临床获益且东部肿瘤协作组（ECOG）体能状态≤2，则符合B部分的入组标准。在B部分，患者按最后一次接受的剂量服用阿法替尼，加用紫杉醇80 mg/m²每周一次，直至疾病进展或出现无法耐受的AE。A部分的主要终点是客观缓解（OR）；次要终点包括疾病控制（DC）、无进展生存期（PFS）和总生存期（OS）。进一步的探索性终点是B部分的OR、DC和PFS。
A部分有18例患者接受了阿法替尼治疗。无患者达到OR；11例患者（61.1%）疾病稳定，6例患者（33.3%）疾病进展。因此，DC率为61.1%（95%置信区间[CI]：35.7，82.7）。8例患者的肿瘤大小较基线下降超过0至<30%。在分析时，16例患者（88.9%）出现疾病进展或死亡。中位PFS为2.76个月（95% CI：1.87，4.60），中位OS为10.02个月（95% CI：8.47，10.08）。所有患者均经历了≥1次AE，最常见的是腹泻（66.7%）和皮疹（33.3%）。没有患者符合B部分的纳入标准，且入组缓慢；因此，该研究终止。
本研究发现阿法替尼对未使用过EGFR-TKI的HER2m+ NSCLC患者无临床获益。
