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Abstract：
BACKGROUND: Osimertinib represents the standard of care for the treatment of advanced non-small-cell lung cancer (NSCLC) harboring classical epidermal growth factor receptor (EGFR) mutations, constituting 80%-90% of all EGFR alterations. In the remaining cases, an assorted group of uncommon alterations of EGFR (uEGFR) can be detected, which confer variable sensitivity to previous generations of EGFR inhibitors, overall with lower therapeutic activity. Data on osimertinib in this setting are limited and strongly warranted.
METHODS: The ARTICUNO study retrospectively evaluated data on osimertinib activity from patients with advanced NSCLC harboring uEGFR treated in 21 clinical centers between August 2017 and March 2023. Data analysis was carried out with a descriptive aim. Investigators collected response data according to RECIST version 1.1 criteria. The median duration of response, progression-free survival (mPFS), and overall survival were estimated by the Kaplan-Meier method.
RESULTS: Eighty-six patients harboring uEGFR and treated with osimertinib were identified. Patients with \'major\' uEGFR, that is, G719X, L861X, and S768I mutations (n = 51), had an overall response rate (ORR) and mPFS of 50% and 9 months, respectively. Variable outcomes were registered in cases with rarer \'minor\' mutations (n = 27), with ORR and mPFS of 31% and 4 months, respectively. Among seven patients with exon 20 insertions, ORR was 14%, while the best outcome was registered among patients with compound mutations including at least one classical EGFR mutation (n = 13). Thirty patients presented brain metastases (BMs) and intracranial ORR and mPFS were 58% and 9 months, respectively. Amplification of EGFR or MET, TP53 mutations, and EGFR E709K emerged after osimertinib failure in a dataset of 18 patients with available rebiopsy.
CONCLUSIONS: The ARTICUNO study confirms the activity of osimertinib in patients with uEGFR, especially in those with compound uncommon-common mutations, or major uEGFR, even in the presence of BMs. Alterations at the E709 residue of EGFR are associated with resistance to osimertinib.
METHODS: The ARTICUNO study retrospectively evaluated data on osimertinib activity from patients with advanced NSCLC harboring uEGFR treated in 21 clinical centers between August 2017 and March 2023. Data analysis was carried out with a descriptive aim. Investigators collected response data according to RECIST version 1.1 criteria. The median duration of response, progression-free survival (mPFS), and overall survival were estimated by the Kaplan-Meier method.
RESULTS: Eighty-six patients harboring uEGFR and treated with osimertinib were identified. Patients with \'major\' uEGFR, that is, G719X, L861X, and S768I mutations (n = 51), had an overall response rate (ORR) and mPFS of 50% and 9 months, respectively. Variable outcomes were registered in cases with rarer \'minor\' mutations (n = 27), with ORR and mPFS of 31% and 4 months, respectively. Among seven patients with exon 20 insertions, ORR was 14%, while the best outcome was registered among patients with compound mutations including at least one classical EGFR mutation (n = 13). Thirty patients presented brain metastases (BMs) and intracranial ORR and mPFS were 58% and 9 months, respectively. Amplification of EGFR or MET, TP53 mutations, and EGFR E709K emerged after osimertinib failure in a dataset of 18 patients with available rebiopsy.
CONCLUSIONS: The ARTICUNO study confirms the activity of osimertinib in patients with uEGFR, especially in those with compound uncommon-common mutations, or major uEGFR, even in the presence of BMs. Alterations at the E709 residue of EGFR are associated with resistance to osimertinib.
摘要：
背景：奥希替尼代表了具有经典表皮生长因子受体（EGFR）突变的晚期非小细胞肺癌（NSCLC）的治疗标准，占所有EGFR改变的80%-90%。在其余案件中,可以检测到一组不常见的EGFR（uEGFR）改变，赋予前几代EGFR抑制剂可变的敏感性，总体治疗活性较低。在这种情况下，奥希替尼的数据是有限的，有充分的理由。
方法：ARTICUNO研究回顾性评估了2017年8月至2023年3月期间在21个临床中心接受uEGFR治疗的晚期NSCLC患者的奥希替尼活性数据。数据分析是以描述性为目的进行的。研究者根据RECIST1.1版标准收集应答数据。反应持续时间的中位数，无进展生存期（mPFS），和总生存期通过Kaplan-Meier方法估计。
结果：确定了86例携带uEGFR并接受奥希替尼治疗的患者。患有主要uEGFR的患者，也就是说,G719X,L861X,和S768I突变（n=51），总有效率（ORR）和mPFS为50％和9个月，分别。在罕见的“次要”突变的病例中登记了可变结果(n=27)，ORR和mPFS为31%和4个月，分别。在7例外显子20插入的患者中，ORR为14%,而最佳结局是在复合突变包括至少一个经典EGFR突变的患者中(n=13).30例患者出现脑转移（BMs），颅内ORR和mPFS分别为58％和9个月，分别。EGFR或MET扩增，TP53突变,和EGFRE709K在奥希替尼失败后出现，在18例患者的数据集中进行了再活检。
结论：ARTICUNO研究证实了奥希替尼在uEGFR患者中的活性，尤其是那些具有复合罕见常见突变的人，或者主要的uEGFR，EGFRE709残基的改变与奥希替尼耐药相关。
方法：ARTICUNO研究回顾性评估了2017年8月至2023年3月期间在21个临床中心接受uEGFR治疗的晚期NSCLC患者的奥希替尼活性数据。数据分析是以描述性为目的进行的。研究者根据RECIST1.1版标准收集应答数据。反应持续时间的中位数，无进展生存期（mPFS），和总生存期通过Kaplan-Meier方法估计。
结果：确定了86例携带uEGFR并接受奥希替尼治疗的患者。患有主要uEGFR的患者，也就是说,G719X,L861X,和S768I突变（n=51），总有效率（ORR）和mPFS为50％和9个月，分别。在罕见的“次要”突变的病例中登记了可变结果(n=27)，ORR和mPFS为31%和4个月，分别。在7例外显子20插入的患者中，ORR为14%,而最佳结局是在复合突变包括至少一个经典EGFR突变的患者中(n=13).30例患者出现脑转移（BMs），颅内ORR和mPFS分别为58％和9个月，分别。EGFR或MET扩增，TP53突变,和EGFRE709K在奥希替尼失败后出现，在18例患者的数据集中进行了再活检。
结论：ARTICUNO研究证实了奥希替尼在uEGFR患者中的活性，尤其是那些具有复合罕见常见突变的人，或者主要的uEGFR，EGFRE709残基的改变与奥希替尼耐药相关。
