Clinical and Translational Oncology Group, Institute of Oncology, Clínica del Country, Bogotá, Colombia.
Foundation for Clinical and Applied Cancer Research - FICMAC, Bogotá, Colombia.
Target Oncol. 2017 Aug;12(4):513-523. doi: 10.1007/s11523-017-0497-2.
Lung cancer harboring epidermal growth factor receptor (EGFR) mutations and treated with EGFR tyrosine kinase inhibitors (TKIs) all eventually develop acquired resistance to the treatment, with half of the patients developing EGFR T790M resistance mutations.
The purpose of this study was to assess histological and clinical characteristics and survival outcomes in Hispanic EGFR mutated lung cancer patients after disease progression.
EGFR mutation-positive lung cancer patients (n = 34) with acquired resistance to the EGFR-TKI erlotinib were identified from 2011 to 2015. Post-progression tumor specimens were collected for molecular analysis. Post-progression interventions, response to treatment, and survival were assessed and compared among all patients and those with and without T790M mutations.
Mean age was 59.4 ± 13.9 years, 65% were never-smokers, and 53% had a performance status 0-1. All patients received erlotinib as first-line treatment. Identified mutations included: 60% DelE19 (Del746-750) and 40% L858R. First-line erlotinib overall response rate (ORR) was 61.8% and progression free survival (PFS) was 16.8 months (95% CI: 13.7-19.9). Acquired resistance mutations identified were T790M mutation (47.1%); PI3K mutations (14.7%); EGFR amplification (14.7%); KRAS mutation (5.9%); MET amplification (8.8%); HER2 alterations (5.9%, deletions/insertions in e20); and SCLC transformation (2.9%). Of patients, 79.4% received treatment after progression. ORR for post-erlotinib treatment was 47.1% (CR 2/PR 14) and median PFS was 8.3 months (95% CI: 2.2-36.6). Median overall survival (OS) from treatment initiation was 32.9 months (95% CI: 30.4-35.3), and only the use of post-progression therapy affected OS in a multivariate analysis (p = 0.05).
Hispanic patients with acquired resistance to erlotinib continued to be sensitive to other treatments after progression. The proportion of T790M+ patients appears to be similar to that previously reported in Caucasians.
携带表皮生长因子受体（EGFR）突变的肺癌患者接受 EGFR 酪氨酸激酶抑制剂（TKIs）治疗后均会最终对治疗产生获得性耐药，其中一半患者会发生 EGFR T790M 耐药突变。
本研究旨在评估 EGFR 突变阳性的肺癌患者在疾病进展后出现获得性 EGFR-TKI 厄洛替尼耐药时的组织学和临床特征及生存结局。
从 2011 年至 2015 年，我们确定了 34 例 EGFR 突变阳性的肺癌患者（n=34），这些患者对 EGFR-TKI 厄洛替尼产生了获得性耐药。对进展后的肿瘤标本进行了分子分析。评估了所有患者以及有和无 T790M 突变患者的进展后干预措施、治疗反应和生存情况，并对其进行了比较。
患者的平均年龄为 59.4±13.9 岁，65%为从不吸烟者，53%的患者表现状态为 0-1 级。所有患者均接受厄洛替尼作为一线治疗。鉴定出的突变包括：60% DelE19（Del746-750）和 40% L858R。一线厄洛替尼的总体缓解率（ORR）为 61.8%，无进展生存期（PFS）为 16.8 个月（95%CI：13.7-19.9）。获得性耐药突变包括 T790M 突变（47.1%）；PI3K 突变（14.7%）；EGFR 扩增（14.7%）；KRAS 突变（5.9%）；MET 扩增（8.8%）；HER2 改变（5.9%，e20 缺失/插入）；和小细胞肺癌转化（2.9%）。有 79.4%的患者在进展后接受了治疗。厄洛替尼治疗后的 ORR 为 47.1%（CR 2/PR 14），中位 PFS 为 8.3 个月（95%CI：2.2-36.6）。从治疗开始的中位总生存期（OS）为 32.9 个月（95%CI：30.4-35.3），只有在多变量分析中，进展后治疗的使用才影响 OS（p=0.05）。
对厄洛替尼产生获得性耐药的西班牙裔患者在疾病进展后继续对其他治疗敏感。T790M+患者的比例似乎与以前在白种人中的报告相似。
