背景:大约10%的EGFR突变(EGFRmuts)并不常见(ucEGFRmuts)。我们旨在收集奥希替尼治疗ucEGFRmuts患者的实际数据。
方法:这是一个多中心,奥希替尼作为首个EGFR抑制剂治疗的ucEGFRmut(外显子20插入除外)转移性NSCLC的回顾性研究.研究人员评估了实体瘤的反应评估标准和神经肿瘤学脑转移的反应评估,脑客观反应率(ORR)。中位无进展生存期(mPFS),中位总生存期,从奥希替尼开始计算中位缓解持续时间(mDOR).收集在抗性处发现的突变。
结果:共纳入60例患者(22个中心,九个国家),平均年龄为64岁,75%的女性,和83%的白种人。最大的亚组是G719X(30%),L861Q(20%),和从头Thr790Met(T790M)(15%)。ORR为61%,mPFS9.5个月,mDOR17.4个月,中位总生存期24.5个月。对于没有并发常见突变或T790M的患者(A组,n=44),ORR为60%,mPFS8.6个月,和mDOR11个月。对于G719X,ORR为47%,mPFS8.8个月,和MDOR9.1个月。对于L861Q,ORR为80%,mPFS16个月,和mDOR16个月。对于从头T790M,ORR为44%,mPFS12.7个月,和mDOR46.2个月。与仅有ucEGFRmut相比,包括常见突变的化合物EGFRmut具有更好的结果。对于13名在神经肿瘤学脑转移-可评估的脑转移中进行反应评估的患者,大脑ORR为46%。对于14名患者,再活检结果进行了分析:4例额外的EGFR突变患者(C797S,D585Y,E709K),三个有新的TP53突变,一个用c-Met扩增,一个有PIK3CA突变,和一个神经内分泌转化。
结论:发现奥希替尼在ucEGFRmut中具有活性,在全身和颅内均具有较高的疾病控制率。确定了几种抗性机制。这份报告包括,据我们所知,同类最大的数据集。
BACKGROUND: Approximately 10% of EGFR mutations (EGFRmuts) are uncommon (ucEGFRmuts). We aimed to collect real-world data about osimertinib for patients with ucEGFRmuts.
METHODS: This is a multicenter, retrospective study of ucEGFRmut (exon 20 insertions excluded) metastatic NSCLC treated with osimertinib as first EGFR inhibitor. The Response Evaluation Criteria in Solid Tumors and response assessment in neuro-oncology brain metastases brain objective response rate (ORR) were evaluated by the investigators. Median progression-free survival (mPFS), median overall survival, and median duration of response (mDOR) were calculated from osimertinib initiation. Mutations found at resistance were collected.
RESULTS: A total of 60 patients were included (22 centers, nine countries), with median age of 64 years, 75% females, and 83% Caucasian. The largest subgroups were G719X (30%), L861Q (20%), and de novo Thr790Met (T790M) (15%). The ORR was 61%, mPFS 9.5 months, mDOR 17.4 months, and median overall survival 24.5 months. Regarding patients with no concurrent common mutations or T790M (group A, n = 44), ORR was 60%, mPFS 8.6 months, and mDOR 11 months. For G719X, ORR was 47%, mPFS 8.8 months, and mDOR 9.1 months. For L861Q, ORR was 80%, mPFS 16 months, and mDOR 16 months. For de novo T790M, ORR was 44%, mPFS 12.7 months, and mDOR 46.2 months. Compound EGFRmut including common mutations had better outcome compared with only ucEGFRmut. For 13 patients with a response assessment in neuro-oncology brain metastases-evaluable brain metastases, brain ORR was 46%. For 14 patients, rebiopsy results were analyzed: four patients with additional EGFR mutation (C797S, D585Y, E709K), three with new TP53 mutation, one with c-Met amplification, one with PIK3CA mutation, and one with neuroendocrine transformation.
CONCLUSIONS: Osimertinib was found to have an activity in ucEGFRmut with a high rate of disease control systemically and intracranially. Several resistance mechanisms were identified. This report comprises, to the best of our knowledge, the largest data set of its kind.