Neoadjuvant Aumonertinib In Potential Resectable Stage Ⅲ EGFR Mutation-positive Lung Adenocarcinoma

Background Primary bronchogenic carcinoma is one of the most common malignancies,and non-small cell lung cancer(NSCLC)is the major pathological type of primary bronchogenic carcinoma,with lung adenocarcinoma being the most common histological subtype.The majority of EGFR mutations are concentrated in exons 18 to21 of its gene,with the most common mutations in lung adenocarcinoma being the deletion mutation in exon 19(approximately 44%)and the L858 R point mutation in exon 21(approximately 41%).For resectable early-stage NSCLC,curative surgery and adjuvant radiotherapy and chemotherapy are still the standard treatment recommended by guidelines.Neoadjuvant therapy can effectively control the primary tumor and metastasis to the mediastinal lymph nodes in potentially resectable locally advanced lung cancer patients,increase the possibility of R0 resection,and reduce the risk of postoperative recurrence.Targeted therapy for EGFR mutations has significant efficacy in advanced lung cancer patients,but the efficacy and long-term prognosis of neoadjuvant targeted therapy for locally advanced lung cancer patients still need further exploration.This study aims to evaluate the efficacy and safety of neoadjuvant treatment with aumonertinib in potentially resectable stage III EGFR mutationpositive NSCLC by exploring the objective response rate,postoperative patient survival,and recurrence.Methods This is a prospective,open-label,single-arm phase II clinical trial aimed at evaluating the efficacy and safety of neoadjuvant treatment with 2-4 cycles of the EGFR tyrosine kinase inhibitor,aumonertinib,in potentially resectable stage III EGFR mutation-positive non-small cell lung cancer patients.The study will enroll a total of56 patients.The primary endpoint of the study is objective response rate(ORR),and the secondary endpoints include pathological complete response rate(p CR),disease-free survival(DFS),overall survival(OS),quality of life(Qo L),health-related quality of life(HRQo L),R0 resection rate,and safety.WES and RNA sequencing analysis to explore the molecular features affected by aumonertinib treatment.Results As of April 2023,a total of 41 patients have been screened and completed at least one tumor assessment in this study.According to RECIST1.1 criteria,among the 41 patients who completed at least one cycle of treatment,30 patients achieved PR after receiving neoadjuvant targeted therapy with aumonertinib,with an ORR of 73.17%and a disease control rate(DCR)of 95.12%.Eight patients underwent curative surgery after treatment,with a surgical R0 resection rate of 100%.Among the surgical patients,one patient achieved pathological complete response(p CR),and two patient achieved major pathological response(MPR),with an overall MPR rate of 37.5%.34 patients(72.34%)experienced treatment-related adverse events(AE)during the treatment process.Among them,89.5% of the adverse events were assessed as grade 1-2,and five patients(10.6%)experienced grade 3-4 adverse reactions.The RNAseq analysis showed that the endothelial cells and VEGF family members(VEGFB and VEGFC)were highly expressed after treatment,which provided a new idea for the subsequent treatment of patients and the design of future clinical trials.Conclusion This study indicates that neoadjuvant targeted therapy with aumonertinib is safe and effective for potentially resectable stage III EGFR-mutant non-small cell lung cancer patients.