Han Yu, Xu Jian-Ming, Duan Hai-Qing, Zhang Yang, Liu Xiao-Qing, Zhang Jing-Sheng
Beijing 307 Hospital Cancer Center, Beijing, People's Republic of China.
Chin J Cancer. 2010 Jan;29(1):69-75. doi: 10.5732/cjc.009.10345.
The effect of gefitinib on advanced non-small cell lung cancer (NSCLC) was various. How to choose the sensitive patients and improve the effect was difficulty in clinic. This study was to assess the correlation of epidermal growth factor receptor (EGFR) mutations and HER2/3 protein expression with the effect of gefitinib on Chinese patients with advanced NSCLC.
From May 2002 to February 2005, a total of 106 Chinese NSCLC patients who had failed at least one chemotherapy regimen were treated with gefitinib 250 mg once a day. The mutations in the exons 18-24 of EGFR gene were detected in the tumor tissues from 106 patients before the treatment of gefitinib, and HER2/3 expression in 84 tumor samples were detected by immunohistochemistry.
Mutation was identified in 32 (30.2%) tumor tissues. Overall remission rate was significantly higher in the HER2 high expression patients than in the HER2 low expression patients (36.8% vs 17.4%, P=0.044). HER2 and HER3 expression levels were not associated with time to progression (TTP) and overall survival (OS). The patients with HER2/3 single high expression had relatively longer TTP and OS than those with HER2/3 single low expression (6.1 vs 9.1 months, P=0.725; 6.1 vs 9.0 months, P=0.862), while those with concomitant HER2/3 high expression had significant longer TTP and OS. EGFR-mutated patients with HER2 expression or high HER2 and HER3 expressions were more sensitive to gefitinib.
EGFR mutations combined with HER2/3 expressions is a significant predictor for gefitinib efficacy on Chinese patients with advanced NSCLC.
吉非替尼对晚期非小细胞肺癌(NSCLC)的疗效各异。临床上如何选择敏感患者并提高疗效存在困难。本研究旨在评估表皮生长因子受体(EGFR)突变及HER2/3蛋白表达与吉非替尼对中国晚期NSCLC患者疗效的相关性。
2002年5月至2005年2月,共106例至少经过一种化疗方案治疗失败的中国NSCLC患者接受吉非替尼250mg每日一次治疗。在吉非替尼治疗前,检测106例患者肿瘤组织中EGFR基因第18 - 24外显子的突变情况,并用免疫组化法检测84例肿瘤样本中的HER2/3表达。
32例(30.2%)肿瘤组织检测到突变。HER2高表达患者的总缓解率显著高于HER2低表达患者(36.8%对17.4%,P = 0.044)。HER2和HER3表达水平与疾病进展时间(TTP)和总生存期(OS)无关。HER2/3单高表达患者的TTP和OS较HER2/3单低表达患者相对较长(6.1对9.1个月,P = 0.725;6.1对9.0个月,P = 0.862),而HER2/3同时高表达患者的TTP和OS显著更长。EGFR突变且伴有HER2表达或HER2和HER3高表达的患者对吉非替尼更敏感。
EGFR突变联合HER2/3表达是吉非替尼对中国晚期NSCLC患者疗效的重要预测指标。