Li Jiaqi, Xie Mengqing, Zhao Ruiying, Qiang Huiping, Chang Qing, Qian Jialin, Lu Haijiao, Shen Yinchen, Han Yuchen, Su Chunxia, Chu Tianqing
Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.
Front Oncol. 2024 Mar 19;14:1357231. doi: 10.3389/fonc.2024.1357231. eCollection 2024.
For patients with EGFR/HER2 exon20 insertions, platinum-containing double-drug chemotherapy is still the standard treatment method. First-generation TKIs have almost no therapeutic activity against EGFR exon 20 insertions. The efficacy of second-and third-generation TKIs is still controversial. Immunotherapy research is scarce, and there is an urgent need for more evidence and new treatment options for this group of patients.
We reviewed patients with advanced NSCLC with EGFR/HER2 exon 20 insertion mutations treated in Shanghai Chest Hospital and Shanghai Pulmonary Hospital from 2015 to 2022 and assessed the efficacy of receiving chemotherapy, anti-angiogenic therapy and immunotherapy, including objective response rate (ORR) and disease control rate (DCR), and compared progression-free survival (PFS) and overall survival (OS).
Of the 126 patients included in the study, 51 patients had EGFR20ins mutations and 7 5 patients had HER2-20ins mutations. In the first-line treatment, bevacizumab + chemotherapy (Beva+Chemo), ICI+chemotherapy (ICI+Chemo), compared with chemotherapy alone (Chemo), ORR: 40% vs 33.3% vs 15% (p=0.0168); DCR: 84% vs 80.9% vs 67.5% (p=0.1817); median PFS: 8.3 vs 7.0 vs 4.6 months (p=0.0032), ICI+Chemo has a trend of benefiting on OS. Stratified analysis showed that compared with chemotherapy, ICI+Chemo was more effective for EGFR20ins mutation with median PFS: 10.3 vs. 6.3m (P=0.013); Beva+Chemo was more effective for HER2-20ins mutation, with a median PFS: 6.6 vs. 4.3m (p=0.030). In the second-line treatment of EGFR20ins mutation, bevacizumab + chemotherapy has a significant advantage in PFS compared with targeted therapy, median PFS:10.8 vs 4.0 months (P=0.016).
For patients with EGFR20ins mutation, compared to chemotherapy, ICI+Chemo prolongs PFS, and after chemotherapy progression, bevacizumab combined with chemotherapy seems better than Furmonertinib-based targeted therapy on PFS. For HER2-20ins mutation, Beva+Chemo may be a better choice.
对于表皮生长因子受体（EGFR）/人表皮生长因子受体2（HER2）外显子20插入突变的患者，含铂双药化疗仍是标准治疗方法。第一代酪氨酸激酶抑制剂（TKIs）对EGFR外显子20插入突变几乎没有治疗活性。第二代和第三代TKIs的疗效仍存在争议。免疫治疗研究较少，迫切需要为这组患者提供更多证据和新的治疗选择。
我们回顾了2015年至2022年在上海胸科医院和上海肺科医院接受治疗的晚期非小细胞肺癌（NSCLC）伴EGFR/HER2外显子20插入突变的患者，并评估了接受化疗、抗血管生成治疗和免疫治疗的疗效，包括客观缓解率（ORR）和疾病控制率（DCR），并比较了无进展生存期（PFS）和总生存期（OS）。
在纳入研究的126例患者中，51例患者有EGFR20ins突变，75例患者有HER2-20ins突变。在一线治疗中，贝伐单抗+化疗（Beva+Chemo）、免疫检查点抑制剂+化疗（ICI+Chemo）与单纯化疗（Chemo）相比，ORR分别为40%、33.3%和15%（p=0.0168）；DCR分别为84%、80.9%和67.5%（p=0.1817）；中位PFS分别为8.3个月、7.0个月和4.6个月（p=0.0032），ICI+Chemo在OS方面有获益趋势。分层分析显示，与化疗相比，ICI+Chemo对EGFR20ins突变更有效，中位PFS为10.3个月对6.3个月（P=0.013）；Beva+Chemo对HER2-20ins突变更有效，中位PFS为6.6个月对4.3个月（p=0.030）。在EGFR20ins突变的二线治疗中，贝伐单抗+化疗在PFS方面比靶向治疗有显著优势，中位PFS为10.8个月对4.0个月（P=0.016）。
对于EGFR20ins突变的患者，与化疗相比，ICI+Chemo可延长PFS，化疗进展后，贝伐单抗联合化疗在PFS方面似乎优于伏美替尼为基础的靶向治疗。对于HER2-20ins突变，Beva+Chemo可能是更好的选择。
