■第三代表皮生长因子受体(EGFR)酪氨酸激酶抑制剂(TKI),奥希替尼,是常见EGFR突变阳性非小细胞肺癌(NSCLC)患者的有效一线治疗方法。然而,几乎所有患者都对治疗产生抗药性。在一些患者中,三级EGFR突变的出现被认为是一种耐药机制。这项研究描述了获得罕见EGFR突变的NSCLC患者,L718Q或G724S,EGFRTKI治疗后。
■这是一个回顾,2021年2月至11月在法国进行的观察性研究,对象是EGFR突变阳性且具有获得性L718Q或G724S突变的NSCLC患者.主要目标是描述肿瘤特征,programming,和治疗中的进展。
■确定了9名合格患者。6例患者对初始EGFRTKI治疗的获得性耐药与T790M出现相关,他随后接受了奥希替尼单药治疗。总的来说,8例患者在某个时间点接受了奥希替尼单药治疗(平均治疗持续时间:18.3个月).随着L718Q或G724S的出现,患者接受化疗(n=4;其中两人随后接受阿法替尼),Nivolumab(n=2),阿法替尼(n=2),或免疫化疗(n=1)。4例患者在L718Q或G724S鉴定后接受阿法替尼治疗,2实现了部分响应,其中一人病情稳定,一人病情进展。治疗时间为1.6-31.7个月。在疾病控制的患者中(n=3),无进展生存期为6.1~31.7个月.其中两名患者以前曾接受过奥希替尼。
■目前,对于奥希替尼耐药突变出现后EGFR突变阳性NSCLC的治疗尚无共识,L718Q或G724S。在这种情况下,阿法替尼似乎是一种有希望的治疗选择。
UNASSIGNED: The third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI),
osimertinib, is an effective first-line therapy for patients with common EGFR mutation-positive non-small cell lung cancer (NSCLC). However, almost all patients become resistant to treatment. In some patients, emergence of tertiary EGFR mutations is implicated as a resistance mechanism. This
study describes patients with NSCLC who acquired the rare EGFR mutations, L718Q or G724S, following EGFR TKI treatment.
UNASSIGNED: This was a retrospective, observational
study undertaken in France from Feb-Nov 2021, in patients with EGFR mutation-positive NSCLC with an acquired L718Q or G724S mutation. Primary objectives were description of tumor characteristics, progression, and progression under treatment.
UNASSIGNED: Nine eligible patients were identified. Acquired resistance to initial EGFR TKI treatment was associated with T790M emergence in six patients, who then received osimertinib monotherapy. Overall, eight patients received
osimertinib monotherapy treatment at some point (average treatment duration: 18.3 months). Following the emergence of L718Q or G724S, patients received chemotherapy (n = 4; two of whom subsequently received afatinib), nivolumab (n = 2), afatinib (n = 2), or immunochemotherapy (n = 1). In the four patients who received afatinib after identification of L718Q or G724S, 2 achieved a partial response, one had stable disease and one had progressive disease. Treatment duration was 1.6-31.7 months. In patients with controlled disease (n = 3), progression-free survival was 6.1-31.7 months. Two of these patients had previously received
osimertinib.
UNASSIGNED: Currently, there is no consensus regarding the treatment of EGFR mutation-positive NSCLC following emergence of the osimertinib resistance mutations, L718Q or G724S. Afatinib appears to be a promising treatment option in this setting.