EGFR mutation analysis for prospective patient selection in AURA3 phase III trial of osimertinib versus platinum-pemetrexed in patients with EGFR T790M-positive advanced non-small-cell lung cancer
EGFR mutation analysis for prospective patient selection in AURA3 phase III trial of osimertinib versus platinum-pemetrexed in patients with EGFR T790M-positive advanced non-small-cell lung cancer
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DOI：
10.1016/j.lungcan.2018.10.027
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发表时间：
2018-12-01
期刊：
影响因子：
5.3
通讯作者：
Wu, Yi-Long
中科院分区：
文献类型：
--
作者：
John, Thomas;Akamatsu, Hiroaki;Wu, Yi-Long
目的：在AURA 3（NCT 02151981）中，与铂类-培美曲塞相比，奥希替尼治疗在表皮生长因子受体（EGFR）T790 M阳性晚期非小细胞肺癌（NSCLC）患者中提供了显著的临床获益，这些患者的肿瘤在既往EGFR-酪氨酸激酶抑制剂治疗期间发生了进展。该回顾性分析调查了来自AURA 3筛选人群的组织样本中T790 M、常见（外显子19缺失和L 858 R）和罕见EGFR突变的检出率。材料和方法：在AURA 3中，合格患者以2：1的比例随机接受口服奥希替尼80 mg每日一次或静脉注射铂类-培美曲塞，每3周一次，最多6个周期。使用cobas（R）EGFR突变检测（第2版）集中检测肿瘤组织样本的EGFR突变。T790 M阳性状态是一个关键的纳入criterions.Results：共820筛选患者有一个有效的EGFR突变检测结果，其中452（55%）是T790 M阳性。T790 M（53% vs 58%）和外显子19缺失（56% vs 63%）的检出率按种族（亚裔vs非亚裔）相似。相反，亚裔患者的L 858 R发生率高于非亚裔患者（39% vs 28%; p = 0.0017）。在总体人群中，与L 858 R突变相比，在外显子19缺失背景下检测到T790 M的患者比例更高（64% vs 47%; p < 0.0001）。在28例（3%）患者中检测到罕见的EGFR突变，包括G719 X（2%），外显子20插入（1%）和S768 I（< 1%）。结论：在AURA 3筛选的EGFR突变阳性的晚期NSCLC患者中，约一半的肿瘤组织中可检测到T790 M，该比率不受种族影响。结果与该患者人群中T790 M检出率的既往报告一致。
Objectives: In AURA3 (NCT02151981), osimertinib treatment provided significant clinical benefit compared with platinum-pemetrexed in patients with epidermal growth factor receptor (EGFR) T790M-positive advanced non-small-cell lung cancer (NSCLC), whose tumors had progressed on previous EGFR-tyrosine kinase inhibitor therapy. This retrospective analysis investigated detection rates for T790M, common (exon 19 deletion and L858R), and rare EGFR mutations in tissue samples from the screened population of AURA3.Materials and methods: In AURA3, eligible patients were randomized 2:1 to receive oral osimertinib 80 mg once daily or intravenous platinum-pemetrexed every 3 weeks for up to six cycles. Tumor tissue samples were centrally tested for EGFR mutations using the cobas (R) EGFR Mutation Test (Version 2). T790M-positive status was a key inclusion criteria.Results: A total of 820 screened patients had a valid EGFR mutation test result, of whom 452 (55%) were T790M-positive. Detection rates were similar by ethnicity (Asian versus non-Asian) for T790M (53% versus 58%) and exon 19 deletions (56% versus 63%). Conversely, the L858R rate was higher among Asian patients versus non-Asian patients (39% versus 28%; p = 0.0017). In the overall population, a higher proportion of patients had T790M detected against a background of exon 19 deletion versus L858R mutations (64% versus 47%; p < 0.0001). Rare EGFR mutations were detected in 28 (3%) patients, including G719X (2%), exon 20 insertion (1%), and S768I ( < 1%).Conclusion: Among AURA3 screened patients with EGFR mutation-positive advanced NSCLC, approximately half had detectable T790M in their tumor tissue, a rate unaffected by ethnicity. Results are consistent with previous reports of T790M detection rate in this patient population.