Choi Yong Won, Jeon So Yeon, Jeong Geum Sook, Lee Hyun Woo, Jeong Seong Hyun, Kang Seok Yun, Park Joon Seong, Choi Jin-Hyuk, Koh Young Wha, Han Jae Ho, Sheen Seung Soo
Department of Hematology-Oncology.
Department of Pathology.
Am J Clin Oncol. 2018 Apr;41(4):385-390. doi: 10.1097/COC.0000000000000282.
Exon 19 deletion and L858R mutation in exon 21 of the epidermal growth factor receptor (EGFR) are both common mutations that predict a good response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC). However, the existence of clinically significant difference in sensitivity to EGFR tyrosine kinase inhibitors among different EGFR mutation subtypes is still a matter of debate.
The outcome of 60 EGFR mutation-positive advanced NSCLC patients who received first-line gefitinib therapy (250 mg/d) was retrospectively analyzed according to EGFR mutation subtypes.
The median progression-free survival (PFS) and overall survival (OS) after the initiation of gefitinib therapy for all patients was 11 and 26 months, respectively. Univariate analysis showed that patients with exon 19 deletion (n=28) had significantly longer median PFS (20 vs. 8 mo, P=0.004) and OS (36 vs. 22 mo, P=0.001) compared with those with L858R mutation (n=25) and uncommon or dual mutations (n=7). Multivariate analysis revealed that exon 19 deletion (P=0.007) was an independent prognostic factor of favorable PFS, with an independent association with poor PFS of male sex (P=0.049). Exon 19 deletion was also independently associated with favorable OS (P<0.0001), whereas male sex (P=0.004) and primary metastatic disease (P=0.032) were independent prognostic factors of poor OS.
The EGFR exon 19 deletion was associated with favorable PFS and OS in patients receiving first-line gefitinib treatment. The EGFR mutation subtype should be considered when making treatment decision or designing clinical trials for chemotherapy-naive, EGFR mutation-positive advanced NSCLC patients.
表皮生长因子受体(EGFR)第19外显子缺失和第21外显子L858R突变均为常见突变,可预测非小细胞肺癌(NSCLC)患者对EGFR酪氨酸激酶抑制剂有良好反应。然而,不同EGFR突变亚型对EGFR酪氨酸激酶抑制剂敏感性的临床显著差异是否存在仍存在争议。
回顾性分析60例接受一线吉非替尼治疗(250mg/d)的EGFR突变阳性晚期NSCLC患者的治疗结果,并根据EGFR突变亚型进行分组。
所有患者开始吉非替尼治疗后的中位无进展生存期(PFS)和总生存期(OS)分别为11个月和26个月。单因素分析显示,与L858R突变患者(n=25)和罕见或双重突变患者(n=7)相比,第19外显子缺失患者(n=28)的中位PFS(20个月对8个月,P=0.004)和OS(36个月对22个月,P=0.001)显著更长。多因素分析显示,第19外显子缺失(P=0.007)是PFS良好的独立预后因素,男性性别与PFS不良独立相关(P=0.049)。第19外显子缺失也与良好的OS独立相关(P<0.0001),而男性性别(P=0.004)和原发性转移疾病(P=0.032)是OS不良的独立预后因素。
接受一线吉非替尼治疗的患者中,EGFR第19外显子缺失与良好的PFS和OS相关。对于未经化疗、EGFR突变阳性的晚期NSCLC患者,在制定治疗决策或设计临床试验时应考虑EGFR突变亚型。