Research on the First-line Efficacy of EGFR-TKIs and Chemotherapy in EGFR Non-hotspot Mutated Non-small Cell Lung Cancer

Background 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. Objective To explore the efficacy of EGFR-TKIs versus chemotherapy in EGFR non-hotspot mutated non-small cell lung cancer patients. Methods 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. Results 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) . Conclusion 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.