National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Precision Medicine Center of Oncology, 235960The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Technol Cancer Res Treat. 2022 Jan-Dec;21:15330338221128414. doi: 10.1177/15330338221128414.
: In non-small cell lung cancer (NSCLC) patients harboring mutations, MET-tyrosine kinase inhibitors (TKIs) have been proven to achieve a good response. However, the relative efficacy of different therapeutics in primary NSCLC patients with amplification and the treatment options for patients harboring acquired amplification after the failure of epidermal growth factor receptor (EGFR)-TKIs remain unclear. In total, 33 patients harboring primary amplification and 9 patients harboring acquired alterations identified by next-generation sequencing were enrolled. A retrospective analysis was conducted to compare the efficacy of different therapeutics. In addition, studies reporting various treatments for patients harboring alterations were included in the meta-analysis. In our cohort of patients harboring primary amplification, crizotinib displayed better efficacy than immunotherapy and chemotherapy, as demonstrated both in first-line ( = .0378) and second-line treatment regimens ( = .0181). The disease control rates for crizotinib, immunotherapy, and chemotherapy were 81.8%, 72.7%, and 63.6%, respectively. In particular, the median progression-free survival (PFS) time after immunotherapy in patients harboring amplification and high programed death ligand 1 (PD-L1) expression (>50%) was only 77.5 days. The meta-analysis revealed that the median PFS times after crizotinib and immunotherapy were 4.57 and 2.94 months, respectively. In patients harboring acquired amplification, chemotherapy plus bevacizumab had superior efficacy (310.0 days vs 73.5 days, = .0360) compared with MET-TKIs ± EGFR-TKIs. Immunotherapy showed a low response in patients harboring alterations, even those with concurrent high PD-L1 expression. MET-TKIs might be an optional treatment with worth-expecting efficacy. However, chemotherapy plus bevacizumab could benefit the subpopulation of patients harboring acquired amplification after the failure of EGFR-TKIs.
在携带 突变的非小细胞肺癌 (NSCLC) 患者中，MET 酪氨酸激酶抑制剂 (TKI) 已被证明可获得良好的疗效。然而，在携带 扩增的原发性 NSCLC 患者中，不同治疗方法的相对疗效以及在表皮生长因子受体 (EGFR)-TKI 治疗失败后携带获得性 扩增患者的治疗选择尚不清楚。 共纳入 33 例经下一代测序确定为原发性 扩增的患者和 9 例携带获得性 改变的患者。进行了回顾性分析以比较不同治疗方法的疗效。此外，还纳入了报告不同治疗方法用于携带 改变的患者的研究进行荟萃分析。 在携带原发性 扩增的患者中，克唑替尼的疗效优于免疫治疗和化疗，在一线治疗（ = .0378）和二线治疗方案中均如此（ = .0181）。克唑替尼、免疫治疗和化疗的疾病控制率分别为 81.8%、72.7%和 63.6%。特别是，在携带 扩增且高程序性死亡配体 1 (PD-L1) 表达 (>50%)的患者中，免疫治疗后的中位无进展生存期 (PFS) 时间仅为 77.5 天。荟萃分析显示，克唑替尼和免疫治疗后中位 PFS 时间分别为 4.57 个月和 2.94 个月。在携带获得性 扩增的患者中，化疗加贝伐珠单抗的疗效优于 MET-TKIs ± EGFR-TKIs（310.0 天比 73.5 天， = .0360）。 在携带 改变的患者中，免疫治疗反应率较低，即使是那些同时具有高 PD-L1 表达的患者也是如此。MET-TKI 可能是一种具有潜在疗效的治疗选择。然而，化疗加贝伐珠单抗可能有益于 EGFR-TKI 治疗失败后携带获得性 扩增的患者亚群。
