Osimertinib for Patients With Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Multicenter, Open-Label, Phase II Trial (KCSG-LU15-09)
Osimertinib for Patients With Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Multicenter, Open-Label, Phase II Trial (KCSG-LU15-09)
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DOI：
10.1200/jco.19.00931
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发表时间：
2020-02-10
影响因子：
45.3
通讯作者：
Ahn, Myung-Ju
中科院分区：
文献类型：
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作者：
Cho, Jang Ho;Lim, Sung Hee;Ahn, Myung-Ju
大约10%的表皮生长因子受体（EGFR）突变阳性的非小细胞肺癌（NSCLC）患者携带罕见突变。在这里，我们报告的疗效和安全性奥希替尼在非小细胞肺癌患者窝藏罕见的EGFR mutations.Patient和方法这是一个多中心，单臂，开放标签，在韩国的II期研究。经组织学证实携带EGFR突变（外显子19缺失、L 858 R和T790 M突变以及外显子20插入除外）的转移性或复发性NSCLC患者有资格参加本研究。根据实体瘤疗效评价标准（RECIST）第1.1版，每6周评估一次主要终点客观缓解率。次要终点为无进展生存期、总生存期、缓解持续时间和安全性。结果2016年3月至2017年10月期间，37例患者入组。除1例患者在开始治疗后撤回知情同意外，所有患者均可评价。中位年龄为60岁，22例（61%）为男性。在患者中，61%的患者接受奥希替尼作为一线治疗。鉴定的突变为G719 X（n = 19; 53%），其次为L 861 Q（n = 9; 25%）、S768 I（n = 8; 22%）和其他（n = 4; 11%）。客观缓解率为50%（36例患者中的18例; 95% CI，33%-67%）。中位无进展生存期为8.2个月（95% CI，5.9 - 10.5个月），未达到中位总生存期。中位缓解持续时间为11.2个月（95% CI，7.7 - 14.7个月）。任何级别的不良事件为皮疹（n = 11; 31%），瘙痒（n = 9; 25%），食欲下降（n = 9; 25%），腹泻（n = 8; 22%），呼吸困难（n = 8; 22%），但所有不良事件都是可控的。结论奥希替尼在携带罕见EGFR突变的NSCLC患者中表现出良好的活性和可控的毒性。(C)2019年美国临床肿瘤学会
PURPOSE Approximately 10% of patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) harbor uncommon mutations. Here, we report the efficacy and safety of osimertinib in patients with NSCLC harboring uncommon EGFR mutations.PATIENT AND METHODS This was a multicenter, single-arm, open-label, phase II study in Korea. Patients with histologically confirmed metastatic or recurrent NSCLC harboring EGFR mutations other than the exon 19 deletion, L858R and T790M mutations, and exon 20 insertion were eligible for the study. The primary end point of objective response rate was assessed every 6 weeks by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary end points were progression-free survival, overall survival, duration of response, and safety.RESULTS Between March 2016 and October 2017, 37 patients were enrolled. All were evaluable except one patient who withdrew consent after starting treatment. Median age was 60 years, and 22 (61%) were male. Among patients, 61% received osimertinib as first-line therapy. The mutations identified were G719X (n = 19; 53%), followed by L861Q (n = 9; 25%), S768I (n = 8; 22%), and others (n = 4; 11%). Objective response rate was 50% (18 of 36 patients; 95% CI, 33% to 67%). Median progression-free survival was 8.2 months (95% CI, 5.9 to 10.5 months), and median overall survival was not reached. Median duration of response was 11.2 months (95% CI, 7.7 to 14.7 months). Adverse events of any grade were rash (n = 11; 31%), pruritus (n = 9; 25%), decreased appetite (n = 9; 25%), diarrhea (n = 8; 22%), and dyspnea (n = 8; 22%), but all adverse events were manageable.CONCLUSION Osimertinib demonstrated favorable activity with manageable toxicity in patients with NSCLC harboring uncommon EGFR mutations. (C) 2019 by American Society of Clinical Oncology