Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are one of the individualized targeted therapeutic options for patients with advanced EGFR mutated non-small cell lung cancer (NSCLC), which can significantly improve the prognosis. However, the response to TKIs changed variously depends on different type of EGFR mutations.

To explore the efficacy of EGFR-TKIs versus chemotherapy in EGFR non-hotspot mutated non-small cell lung cancer patients.

Ninety patients with postoperative recurrent or advanced NSCLC during April 2012 to June 2019 were collected from the Fourth Hospital of Hebei Medical University, of whom were confirmed with EGFR non-hotspot mutations. Patients were divided into first-line EGFR-TKIs treatment group and first-line chemotherapy group depended on first-line treatments. All patients were followed up by telephone or by reviewing in-patient and out-patient cases to obtain their prognosis information. The deadline for follow-up was March 31, 2024. The curative effect, progression-free survival (PFS) and overall survival (OS) were observed.

Among 90 patients, there were 52 cases in EGFR-TKIs treatment group and 38 cases in first-line chemotherapy group. There were 16 patients with postoperative recurrence and metastasis, and 74 patients with initial stage ⅢB-Ⅳ diagnosis. Among the patients with EGFR non-hotspot mutations, there were 51 cases of single gene mutation and 39 cases of compound mutations. After progression of first-line EGFR-TKIs treatment, there were 8 patients treated with EGFR-TKIs and 9 patients treated with chemotherapy. After progression of first-line chemotherapy, 8 patients were treated with EGFR-TKIs, 16 patients with chemotherapy and 1 patient with immunotherapy. The PFS of patients with different subtypes of EGFR non-hotspot mutations who received first-line EGFR-TKIs treatment was statistically significant (χ²=24.26, P<0.001). Compared with the first-line chemotherapy group, PFS and OS in the first-line EGFR-TKIs treatment group were significantly different (P<0.05). Among the patients with single mutation, there was significant difference in PFS and OS between the first-line EGFR-TKIs treatment group and the first-line chemotherapy group (P<0.05). Among the patients with compound mutation, there was significant difference in PFS between the irst-line EGFR-TKIs treatment group and the first-line chemotherapy group (P<0.05). There was no significant difference in OS between the first-line EGFR-TKIs treatment group and the first-line chemotherapy group (P>0.05). Among the patients after progression of first-line chemotherapy, the median PFS of second-line EGFR-TKIs treatment (8 cases) and chemotherapy (16 cases) was 11.3 months and 5.6 months, respectively. There was a significant difference of PFS between second-line EGFR-TKIs treatment group and chemotherapy group (χ²=7.487, P=0.006) .

In postoperative recurrent or advanced NSCLC with non-hotspot EGFR mutations, there was a difference in survival between patients with EGFR ex20ins and E20 S768I mutations and patients with other mutation types treated with first-line EGFR-TKIs treatment. However, in all mutation, treatment with first-line EGFR-TKIs significantly prolonged patient survival compared with first-line chemotherapy.

表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）是晚期表皮生长因子受体（EGFR）突变型非小细胞肺癌（NSCLC）患者个体化靶向治疗方案之一，可显著改善患者的预后。然而不同类型EGFR的突变对EGFR-TKIs治疗的反应不同。

比较EGFR非热点突变型NSCLC一线应用EGFR-TKIs及化疗的疗效。

选取2012年4月—2019年6月在河北医科大学第四医院接受治疗的术后复发或晚期NSCLC患者，并确认为EGFR非热点突变型患者共90例。以患者一线治疗方案将患者分为一线EGFR-TKIs治疗组和一线化疗组。收集患者的一般资料及EGFR基因突变情况。所有患者通过电话进行随访或复查住院及门诊病例获得患者预后情况，随访截止时间为2024-03-31。观察并比较患者疗效及无进展生存期（PFS）和总生存期（OS）。

90例患者中一线EGFR-TKIs治疗组52例，一线化疗组38例。术后复发转移患者16例，初诊分期为ⅢB~Ⅳ期患者74例。EGFR非热点突变患者中，单基因突变51例，复合突变39例。一线EGFR-TKIs治疗进展后二线EGFR-TKIs治疗患者8例，二线化疗患者9例。一线化疗进展后二线EGFR-TKIs治疗患者8例，二线化疗患者16例，免疫治疗患者1例。EGFR非热点突变不同亚型接受一线EGFR-TKIs治疗的患者PFS比较，差异有统计学意义（χ²=24.26，P<0.001）。一线EGFR-TKIs治疗组与一线化疗组的PFS、OS比较，差异有统计学意义（P<0.05）。在单突变亚型患者中，一线EGFR-TKIs治疗组与一线化疗组的PFS、OS比较，差异有统计学意义（P<0.05）。在复合位点突变患者中，一线EGFR-TKIs治疗组与一线化疗组的PFS比较，差异有统计学意义（P<0.05）；一线EGFR-TKIs治疗组与一线化疗组的OS比较，差异无统计学意义（P>0.05）。在一线化疗进展后的患者中，二线EGFR-TKIs治疗（8例）与化疗（16例）的中位PFS分别为11.3个月和5.6个月，二线EGFR-TKIs治疗与化疗患者PFS比较，差异有统计学意义（χ²=7.487，P=0.006）。

在EGFR非热点突变型术后复发或晚期NSCLC中，EGFR ex20ins和E20 S768I突变患者与其他突变类型患者接受一线EGFR-TKIs治疗后的生存期存在差异。而在各突变亚型中，与一线化疗相比，一线EGFR-TKIs治疗均明显延长了患者的生存时间。