Division of Thoracic Oncology, European Institute of Oncology, IRCCS, 20141 Milan, Italy.
Department of Public Health, University of Naples Federico II, 80131 Naples, Italy.
Curr Oncol. 2022 Jan 9;29(1):255-266. doi: 10.3390/curroncol29010024.
Compound epidermal growth factor receptor () mutations represent a heterogeneous subgroup of non-small cell lung cancer (NSCLC) patients with uncommon mutations. We conducted a systematic review to investigate the available data on this patients' subgroup. Overall, we found a high heterogeneity in the incidence of compound mutations (4-26% of total mutant cases), which is dependent on the different testing methods adopted and the specific mutations considered. In addition, the relative incidence of distinct compound subclasses identified is reported with extreme variability in different studies. Preclinical and clinical data, excluding exon 20 p.T790M compound mutations, show good responses with EGFR tyrosine kinase inhibitors (TKIs) (combined common mutations: response rate (RR) ≥ 75% with either first- or second-generation TKIs; combined common plus uncommon: RR 40-80% and 100% with first-generation TKIs and afatinib, respectively; combined uncommon: RR 20-70%, ~80% and ~75% with first-generation TKIs, afatinib and osimertinib, respectively). Overall, data are consistent in supporting the use of EGFR TKIs in treating compound mutations, taking into account different sensitivity profile of accompanying mutations for selecting the most adequate EGFR TKI for individual patients.
复合表皮生长因子受体（）突变代表非小细胞肺癌（NSCLC）患者中一个具有罕见突变的异质亚组。我们进行了系统评价，以调查该患者亚组的现有数据。总体而言，我们发现复合突变的发生率存在很高的异质性（总突变病例的 4-26%），这取决于采用的不同检测方法和考虑的特定突变。此外，不同研究报告的不同复合亚类的相对发生率存在极大的可变性。除了外显子 20 p.T790M 复合突变外，临床前和临床数据显示表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）具有良好的反应（联合常见突变：第一代或第二代 EGFR-TKIs 的缓解率（RR）≥75%；联合常见加罕见：第一代 TKI 和阿法替尼的 RR 为 40-80%和 100%；联合罕见：第一代 TKI、阿法替尼和奥希替尼的 RR 分别为 20-70%、约 80%和约 75%）。总体而言，数据一致支持在治疗复合突变时使用 EGFR-TKIs，同时考虑到伴随的突变对选择最适合个体患者的 EGFR-TKI 的敏感性不同。
