Institute of Oncology, Chaim Sheba Medical Center, Ramat Gan, Israel; School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Cancer Center, Soroka University Medical Center, Beer Sheva, Israel; Current Address: Shaare Zedek Medical Center, Jerusalem, Israel.
J Thorac Oncol. 2023 Feb;18(2):169-180. doi: 10.1016/j.jtho.2022.10.004. Epub 2022 Oct 25.
Approximately 10% of EGFR mutations (EGFRmuts) are uncommon (ucEGFRmuts). We aimed to collect real-world data about osimertinib for patients with ucEGFRmuts.
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.
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.
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.
大约 10%的表皮生长因子受体突变（EGFRmut）是不常见的（ucEGFRmut）。我们旨在收集有关 ucEGFRmut 患者使用奥希替尼的真实世界数据。
这是一项多中心、回顾性研究，纳入了接受奥希替尼作为一线 EGFR 抑制剂治疗的不常见（排除外显子 20 插入）转移性 NSCLC 患者。研究者评估了实体瘤反应评估标准和神经肿瘤脑转移的客观颅内缓解率（ORR）。从奥希替尼开始计算中位无进展生存期（mPFS）、中位总生存期和中位缓解持续时间（mDOR）。收集耐药时发现的突变。
共纳入 60 例患者（22 个中心，9 个国家），中位年龄为 64 岁，75%为女性，83%为白种人。最大的亚组是 G719X（30%）、L861Q（20%）和新出现的 Thr790Met（T790M）（15%）。ORR 为 61%，mPFS 为 9.5 个月，mDOR 为 17.4 个月，中位总生存期为 24.5 个月。对于无同时存在常见突变或 T790M 的患者（A 组，n=44），ORR 为 60%，mPFS 为 8.6 个月，mDOR 为 11 个月。G719X 的 ORR 为 47%，mPFS 为 8.8 个月，mDOR 为 9.1 个月。L861Q 的 ORR 为 80%，mPFS 为 16 个月，mDOR 为 16 个月。新出现的 T790M 的 ORR 为 44%，mPFS 为 12.7 个月，mDOR 为 46.2 个月。与仅有 ucEGFRmut 相比，复合 EGFRmut 包括常见突变的患者具有更好的预后。在 13 例可评估颅内转移的神经肿瘤脑转移患者中，颅内 ORR 为 46%。对 14 例患者的活检结果进行了分析：4 例患者存在额外的 EGFR 突变（C797S、D585Y、E709K），3 例患者存在新的 TP53 突变，1 例存在 c-Met 扩增，1 例存在 PIK3CA 突变，1 例存在神经内分泌转化。
奥希替尼在 ucEGFRmut 中具有较高的疾病控制率，全身和颅内均有较高的疾病控制率。确定了几种耐药机制。本报告是迄今为止同类数据中最大的数据集。
