EGFR罕见突变非小细胞肺癌患者的临床病理特征及治疗效果
Clinicopathological Characteristics and Therapeutic Effect of Patients with Non-small Cell Lung Cancer and Uncommon EGFR Mutations
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摘要:目的 探讨表皮生长因子受体(EGFR)基因罕见突变非小细胞肺癌(NSCLC)患者的临床病理特征及治疗效果。方法 采用荧光定量PCR法检测674例NSCLC中EGFR基因状态, 分析EGFR罕见突变与临床病理特征的相关性。结果 EGFR突变阳性率为47.92%, 其中EGFR罕见突变率为5.19%, 包括ex18 G719 A/S/C (G719X)(1.63%)、ex20ins (1.04%)、ex21 L861Q (0.74%)、含一个以上EGFR突变位点的复合突变(1.78%)。相关性分析显示, EGFR罕见突变更多见于女性、无吸烟史、高-中分化、腺癌患者, 易发生脑、骨转移(均P < 0.05);与常见敏感突变相比, 各临床病理特征比较差异均无统计学意义(均P > 0.05)。35例EGFR罕见突变患者中有31例获得随访资料, 中位随访时间10个月, 其中23例为晚期患者, 8例G719X突变晚期患者中, 7例一线使用EGFR-酪氨酸激酶抑制剂(EGFR-TKIs)(其中5例为阿法替尼), 中位PFS为12个月, 1例采用培美曲塞加卡铂化疗方案, PFS为7个月, 低于TKI组; 4例L861Q晚期患者中1例未治疗, 其余3例一线使用TKI, 中位PFS为8个月, 其中使用阿法替尼及贝伐珠单抗靶向治疗的患者, 随访11个月疾病仍稳定; 2例EGFR ex20ins晚期患者行化疗及贝伐珠单抗治疗; 9例复合突变晚期患者使用TKI治疗, 其中5例含T790M的复合突变患者使用三代TKI, 中位PFS大于10个月。结论 EGFR各罕见突变类型与临床病理特征的相关性不尽相同, 晚期EGFR罕见突变(除EGFR ex20ins外)患者, 临床一线治疗一般选择TKI, 其中具有G719X、L861Q突变的晚期NSCLC患者, 推荐使用阿法替尼; 含T790M的复合突变患者三代TKI有显著疗效。Abstract:Objective To investigate the clinicopathological characteristics and treatment effect of patients with non-small cell lung cancer (NSCLC) and uncommon epidermal growth factor receptor (EGFR) gene mutations.Methods Real-time fluorescence quantitative PCR was used to detect the mutation of EGFR in 674 samples of patients with NSCLC.The correlation between uncommon EGFR mutations and clinicopathological characteristics was analyzed.Results The EGFR mutation rate was 47.92%, of which the incidence of uncommon EGFR mutations was 5.19%, showed the presence of ex18 G719 A/S/C (G719X)(1.63%), ex20ins (1.04%), ex21 L861Q (0.74%), and compound mutations (1.78%).Correlation analysis showed that uncommon EGFR mutations were more common in women, non-smokers, patients with high-medium differentiation and adenocarcinoma, and patients were more prone to brain and bone metastasis (all P < 0.05).NSCLC with uncommon EGFR mutations showed no significant differences in clinical and pathological features compared with those with common sensitive mutations (all P > 0.05).Follow-up information was available on 31 patients, with a median follow-up time of 10 months, of which 23 were in advanced stage.Among eight patients with G719X mutation in late stage, seven patients used EGFR tyrosine kinase inhibitor (EGFR TKIs)(five of them used afatinib) in the first line and had a median PFS of 12 months; one patient received chemotherapy with pemetrexed and carboplatin and had PFS of seven months, which was lower than that of the TKI group.Among four patients with L861Q mutation in late stage, one patient was untreated and the three remaining were treated with TKI in the first line and had a median PFS of eight months.The patient who was treated with afatinib and bevacizumab was still stable after 11 months of follow-up.Two patients with EGFR ex20ins in advanced stage were treated with chemotherapy and bevacizumab.Nine patients with compound mutations in advanced stage were treated with TKI; among which, five patients harboring T790M compound mutations were treated with third-generation TKI and had a median PFS of more than 10 months.Conclusion The correlation between specific uncommon EGFR mutation and clinical pathological characteristics varies.For advanced patients with uncommon EGFR mutations (except for ex20ins), TKI is generally chosen as the first-line clinical treatment.Afatinib is recommended for advanced NSCLC patients with G719X and L861Q mutations.Third-generation TKI has significant efficacy in patients with complex mutations containing T790M.
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