U.S. Food and Drug Administration approval summary: Erlotinib for the first-line treatment of metastatic non-small cell lung cancer with epidermal growth factor receptor exon 19 deletions or exon 21 (L858R) substitution mutations

Oncologist. 2014 Jul;19(7):774-9. doi: 10.1634/theoncologist.2014-0089. Epub 2014 May 27.


On May 14, 2013, the U.S. Food and Drug Administration approved erlotinib (Tarceva, Astellas Pharma Inc., Northbrook, IL, http://www.us.astellas.com/) for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations. This indication for erlotinib was approved concurrently with the cobas EGFR Mutation Test (Roche Molecular Systems, Inc., Basel, Switzerland, http://www.molecular.roche.com), a companion diagnostic test for patient selection. The approval was based on clinically important improvements in progression-free survival (PFS) and objective response rate (ORR) and an acceptable toxicity profile demonstrated in a multicenter, open label trial enrolling 174 patients with metastatic NSCLC whose tumors had EGFR mutations as determined by a laboratory-developed test. Patients were randomized (1:1) to receive erlotinib (150 mg/day) or platinum-based doublet chemotherapy. The primary endpoint was investigator-assessed PFS. Secondary endpoints included overall survival (OS) and ORR. Superior PFS (hazard ratio [HR] 0.34; 95% confidence interval [CI]: 0.23, 0.49; p < .001) and ORR (65% vs. 16%) were observed in the erlotinib arm. Median PFS was 10.4 months and 5.2 months in the erlotinib and chemotherapy arms, respectively. There was no difference in OS (HR 0.93; 95% CI: 0.64, 1.35) with median OS of 22.9 months and 19.5 months in the erlotinib and chemotherapy arms, respectively. The most frequent (≥30%) adverse reactions in the erlotinib-treated patients were rash, diarrhea, asthenia, cough, dyspnea, and decreased appetite. The most frequent (≥5%) grade 3 and 4 adverse reactions were rash and diarrhea.

[仅摘要] 摘要

2013 年 5 月 14 日,美国食品药品监督管理局批准将厄洛替尼(特罗凯,安斯泰来制药公司,伊利诺伊州诺斯布鲁克市,http://www.us.astellas.com/)作为一线药物用于治疗表皮生长因子受体 (EGFR) 外显子 19 缺失或外显子 21 (L858R)替换突变的转移性非小细胞肺癌 (NSCLC) 患者。在厄洛替尼获准用于这一适应症的同时,与厄洛替尼伴随使用的诊断性患者筛查试剂盒——cobas EGFR 突变检测试剂盒(罗氏分子系统公司,瑞士巴塞尔,http://www.molecular.roche.com)——也获得了批准。FDA 的这一批准基于一项多中心、开放标签研究的结果。这项研究共纳入了 174 名被实验室开发的试剂盒判定为存在 EGFR 突变的 NSCLC 患者,其结果表明,厄洛替尼可显著提高患者的无进展生存期 (PFS) 和客观缓解率 (ORR),且毒性谱处在容许范围之内。研究中,患者被随机分入两组 (1:1),分别接受厄洛替尼(150 mg/天)或含铂两药化疗。研究的主要终点为研究者评定的 PFS。次要终点包括总生存期 (OS) 和 ORR。厄洛替尼组的 PFS [风险比(HR):0.34;95% 置信区间(CI):0.23,0.49;p < 0.001]和 ORR(两组分别为 65% vs. 16%)均优于化疗组。厄洛替尼组和化疗组的中位 PFS 分别为 10.4 和 5.2 个月。两组的 OS 并不存在显著差异 (HR 0.93; 95% CI: 0.64, 1.35),其中厄洛替尼组的中位 OS 为 22.9 个月,化疗组为 19.5 个月。厄洛替尼组患者的最常见 (≥30%) 不良反应为皮疹、腹泻、虚弱、咳嗽、呼吸困难和食欲下降。最常见 (≥5%) 的 3 和 4 级不良反应为皮疹和腹泻。The Oncologist 2014;19:774–779

Keywords: EGFR mutations; Erlotinib; FDA; Lung cancer.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / enzymology
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Disease-Free Survival
  • Drug Approval*
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Erlotinib Hydrochloride
  • Exons
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / genetics
  • Male
  • Middle Aged
  • Mutation
  • Quinazolines / therapeutic use*
  • Treatment Outcome
  • United States
  • United States Food and Drug Administration
  • Young Adult


  • Quinazolines
  • Erlotinib Hydrochloride
  • EGFR protein, human
  • ErbB Receptors