高剂量奥希替尼治疗晚期EGFR 20号外显子突变阳性的NSCLC:来自2期多中心POSITION20试验的结果

SCI

9 July 2022

High dose osimertinib in patients with advanced stage EGFR exon 20 mutation-positive NSCLC: results from the phase 2 multicenter POSITION20 trial

(LUNG CANCER; IF:6.08)

• Zwierenga F, van Veggel B, Hendriks LEL et al. High dose osimertinib in patients with advanced stage EGFR exon 20 mutation-positive NSCLC: Results from the phase 2 multicenter POSITION20 trial. Lung Cancer 2022; 170: 133-140. DOI: 10.1016/j.lungcan.2022.06.012

• Corresponding author:Fenneke Zwierenga, MD、University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands 、E-mail: f.zwierenga@umcg.nl

Introduction 介绍

Patients with life-threatening advanced non-small cell lung cancer (NSCLC) who harbor an exon 20 deletion and/or insertion mutation (EGFRex20+) have limited effective treatment options. The high dose 3rd generation tyrosine kinase inhibitor (TKI) osimertinib shows promising in vitro activity in EGFRex20+ NSCLC tumors.

具有20外显子缺失和/或插入突变(EGFRex20+)的危及生命的晚期非小细胞肺癌(NSCLC)患者的有效治疗选择有限。高剂量第三代酪氨酸激酶抑制剂(TKI)奥希替尼在EGFR 20号外显子突变的NSCLC肿瘤中显示出良好的体外活性。

Methods方法

The POSITION20 is a single arm phase II, multicenter study investigating 160 mg osimertinib in patients with EGFRex20+, T790M negative NSCLC. We allowed patients to be treatment naïve and to have asymptomatic brain metastases. The primary endpoint was overall response rate (ORR). Secondary outcomes were duration of response (DoR), progression free survival (PFS), overall survival (OS), and treatment related adverse events (trAEs).

POSITION20是一项单臂II期、多中心研究，研究对象为EGFR ex20+、T790M阴性的NSCLC患者，服用160 mg奥希替尼。我们允许患者接受初始治疗，并有无症状的脑转移。主要终点为总体缓解率(ORR)。次要结果为缓解持续时间(DoR)、无进展生存期(PFS)、总生存期(OS)和治疗相关不良事件(trAEs)。

Results 结果

From June 2018 to October 2021, 25 patients were enrolled across five centers in the Netherlands. The median age was 70 years (range, 47-87), 20 patients (80%) were women, and the median number of previous lines of therapy was 1 (range, 0–3). The exon 20 mutations were clustered between A763 and L777. The most common exon 20 mutations were p.(N771_H773dup) (n = 3) and p.(A767_V769dup) (n = 3). The ORR was 28% (95% CI, 12-49%), including seven partial responses, with a median DoR of 5.3 months (range, 2.7-27.6). The median PFS was 6.8 months (95% CI, 4.6-9.1) and the median OS was 15.2 months (95% CI, 14.3-16.0). The most common trAEs were diarrhea (72%), dry skin (44%), and fatigue (44%). The primary reason for discontinuation was progressive disease in 14 patients (56%).

2018年6月至2021年10月，荷兰5个中心招募了25名患者。中位年龄为70岁(范围47-87)，20例(80%)患者为女性，既往治疗线中位数为1(范围0-3)。外显子20突变集中在A763和L777之间。最常见的外显子20突变为p.(N771_H773dup) (n = 3)和p.(A767_V769dup) (n = 3)， ORR为28% (95% CI, 12-49%)，包括7个部分缓解，中位DoR为5.3个月(范围2.7-27.6)。中位PFS为6.8个月(95% CI 4.6-9.1)，中位OS为15.2个月(95% CI 14.3-16.0)。最常见的治疗相关不良事件为腹泻(72%)、皮肤干燥(44%)和疲劳(44%)。14例患者(56%)停用的主要原因是进展性疾病。

Conclusion 结论

The POSITION20 study showed modest antitumor activity in patients with EGFRex20+ NSCLC treated with 160 mg osimertinib, with a confirmed ORR of 28% and acceptable toxicity

POSITION20研究显示，160 mg奥希替尼治疗EGFRex20+ NSCLC患者，具有适度的抗肿瘤活性，ORR为28%，毒性程度可接受。