National Koranyi Institute of TB and Pulmonology, Piheno ut 1, Budapest, H-1122, Hungary.
Division of Pulmonology, University of Pecs, Pecs, Hungary.
BMC Cancer. 2018 May 25;18(1):598. doi: 10.1186/s12885-018-4283-z.
Erlotinib is approved for the first line treatment of epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer. Since the number of prospective studies in Caucasian patients treated in routine clinical setting is limited we conducted a multicenter, phase IV clinical trial to determine the efficacy and safety of erlotinib and to demonstrate the feasibility of the validated standardized companion diagnostic method of EGFR mutation detection.
651 chemonaive, cytologically or histologically verified advanced stage lung adenocarcinoma patients from Hungary, Turkey and Latvia were screened for exon19 microdeletions and exon21 L858R EGFR mutations using the companion diagnostic EGFR test. EGFR mutation-positive, locally advanced or metastatic lung adenocarcinoma patients received as first line treatment erlotinib at 150 mg/day. The primary endpoint was progression-free survival (PFS).
62 EGFR mutation-positive patients (9.5% of screened) were included in the safety/intent-to-treat cohort. Median PFS was 12.8 months (95%CI, 9.9-15.8), objective response rate and one-year survival was 66.1% and 82.5%, respectively. Most frequent treatment related adverse events were diarrhoea and rash. Eastern Oncology Cooperative Group Performance Status (ECOG PS), smoking status and M1a/M1b disease stage were significant prognosticators of PFS (p = 0.017, p = 0.045 and p = 0.002, respectively). There was no significant difference in PFS between the subgroups stratified by gender, age or exon19 vs exon21 mutation.
Our study confirmed the efficacy and safety of first line erlotinib monotherapy in Caucasian patients with locally advanced or metastatic lung adenocarcinoma carrying activating EGFR mutations based on the screening with the approved companion diagnostic procedure.
ClinicalTrials.gov Identifier: NCT01609543.
厄洛替尼获批用于治疗表皮生长因子受体（EGFR）突变阳性的非小细胞肺癌的一线治疗。由于在常规临床环境中治疗的白种人患者进行的前瞻性研究数量有限，我们进行了一项多中心、四期临床试验，以确定厄洛替尼的疗效和安全性，并证明经验证的 EGFR 突变检测伴随诊断方法的可行性。
来自匈牙利、土耳其和拉脱维亚的 651 名未经化疗、经细胞学或组织学证实的晚期肺腺癌患者接受了伴随诊断 EGFR 检测，以筛选外显子 19 微缺失和外显子 21 L858R EGFR 突变。EGFR 突变阳性的局部晚期或转移性肺腺癌患者接受厄洛替尼 150mg/天作为一线治疗。主要终点是无进展生存期（PFS）。
62 名 EGFR 突变阳性患者（筛选出的患者的 9.5%）被纳入安全性/意向治疗队列。中位 PFS 为 12.8 个月（95%CI，9.9-15.8），客观缓解率和一年生存率分别为 66.1%和 82.5%。最常见的与治疗相关的不良事件是腹泻和皮疹。东部肿瘤协作组表现状态（ECOG PS）、吸烟状态和 M1a/M1b 疾病分期是 PFS 的显著预后因素（p=0.017、p=0.045 和 p=0.002）。根据性别、年龄或外显子 19 与外显子 21 突变分层的亚组之间，PFS 无显著差异。
我们的研究证实了基于经批准的伴随诊断程序进行筛选，在携带激活 EGFR 突变的局部晚期或转移性肺腺癌白种人患者中，一线厄洛替尼单药治疗的疗效和安全性。
ClinicalTrials.gov 标识符：NCT01609543。
