Exploring the efficacy and safety of firmonertinib combined with anlotinib and platinum-based doublet chemotherapy as neoadjuvant therapy in patients with EGFR-mutant resectable 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
29
EGFR-TKI: Firmonertinib 80mg daily Antiangiogenic drugs: Anlotinib 8-12mg daily, D1-14 and of 21-day cycles Chemotherapy: pemetrexed plus carboplatin on Day 1 and of 21-day cycles (every 3 weeks) for 3 cycles
Hubei Cancer Hospital
Wuhan, Hubei, China
MPR rate
The proportion of patients with ≤10% residual viable tumor cells in the primary tumor, as assessed by histopathological examination of the resected surgical specimen.
Time frame: At the time of definitive surgery
pCR rate
The proportion of patients with no residual invasive tumor in the primary tumor and all sampled lymph nodes, as assessed by histopathological examination of the resected surgical specimen.
Time frame: At the time of definitive surgery
Complete resection rate (R0 resection)
The proportion of patients who achieve a complete (R0) resection of all known disease, as determined by the surgeon and pathologist at the time of definitive surgical resection.
Time frame: At the time of definitive surgery
Event-Free Survival (EFS)
Patients alive and free from disease recurrence, progression, or death from any cause after study enrollment
Time frame: Through study completion, an average of 4 years
Overall Survival (OS)
Patients alive after study enrollment
Time frame: Through study completion, an average of 4 years
AE
The incidence and severity of treatment-emergent adverse events (TEAEs) and treatment-related adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Time frame: From the first dose of study treatment up to 30 days after the last dose of study treatment
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