Neoadjuvant Therapy With Firmonertinib Combined With Anlotinib and Platinum-Based Doublet Chemotherapy for Resectable EGFR-Mutated NSCLC

Multiple ongoing clinical trials are investigating the efficacy and safety of the new generation EGFR-TKI in neoadjuvant therapy. The research on neoadjuvant targeted therapy is still in its early stages, and the optimal treatment time is still unclear. Additional data from ongoing clinical trials will be crucial in determining the optimal duration of neoadjuvant targeted therapy. Compared with neoadjuvant immunotherapy, preliminary data suggest that the MPR or pathological complete response (pCR) rate of neoadjuvant targeted therapy may be lower, while other efficacy endpoints (R0 resection rate, reduction in progression, Event Free Survival (EFS), DFS, PFS) are comparable. Firmonertinib is a third-generation EGFR-TKI developed by Shanghai Ailisi Pharmaceutical Technology Co., Ltd. It can simultaneously target EGFR sensitive mutations and Thr790Met mutations \[37\]. FURLONG research has shown that in the first-line treatment of EGFR mutation positive NSCLC patients in China, fumatinib is superior to first generation EGFR-TKI gefitinib in terms of PFS, and patients have better tolerance. This benefit is consistent in most pre-designated subgroups, including patients with central nervous system metastases. Anlotinib is a small molecule multi-target TKI independently developed by China Zhengda Tianqing Pharmaceutical Group Co., Ltd. It can effectively inhibit kinases such as VEGFR, PDGFR, FGFR, and c-Kit, and has anti-tumor angiogenesis and tumor growth inhibition effects. The oral presentation of the FLALTER study at the 2022 European Society for Medical Oncology (ESMO) annual meeting showed that the combination of anlotinib and gefitinib significantly prolonged the median progression free survival (PFS) of patients with metastatic EGFR mutant NSCLC compared to the gefitinib monotherapy group. The preliminary results of multiple ongoing clinical trials indicate that the ORR of anlotinib combined with third-generation EGFR-TKI for the treatment of EGFR mutant advanced NSCLC ranges from 65.20% to 96.15%, demonstrating the enormous potential of the combination therapy. The aim of this study is to investigate the efficacy and safety of neoadjuvant firmonertinib combined with anlotinib and chemotherapy in the treatment of resectable EGFR mutation positive NSCLC.