Evaluate the efficacy and safety of neoadjuvant furmonertinib combined with anlotinib and chemotherapy in patients with resectable stage II-III EGFR mutation-positive non-small cell lung cancer.
Furmonertinib is a third-generation EGFR-TKI developed by Shanghai Allist Pharmaceuticals, capable of targeting both EGFR-sensitive mutations and the Thr790Met mutation. The FURLONG study demonstrated that, in Chinese patients with EGFR-mutant NSCLC, first-line treatment with furmonertinib showed superior PFS and better tolerability compared to the first-generation EGFR-TKI gefitinib, particularly in patients with central nervous system metastases. Anlotinib is a multi-target TKI developed by Chia Tai Tianqing Pharmaceutical, which can inhibit multiple kinases, including VEGFR, PDGFR, FGFR, and c-Kit, exhibiting anti-tumor angiogenesis and tumor growth inhibition effects. The FLALTER study showed that anlotinib combined with gefitinib significantly prolonged median PFS in treatment-naive metastatic EGFR-mutant NSCLC patients. Preliminary results from ongoing clinical trials indicate that the ORR of anlotinib combined with third-generation EGFR-TKIs in advanced NSCLC ranges from 65.20% to 96.15%. Compared to adjuvant therapy, neoadjuvant therapy for resectable NSCLC offers several potential benefits, including improved patient tolerance, early control of microscopic metastatic disease through systemic treatment, and the potential for less extensive surgical resection, leading to an increased rate of complete (R0) resection. So far, the exploration of EGFR-TKIs, including gefitinib, erlotinib, and osimertinib, in the field of neoadjuvant therapy has been undertaken. An open-label, single-arm Phase 2 study (NCT00188617) demonstrated that gefitinib is a safe and feasible option for unselected patients with Stage I NSCLC, with an ORR of 11%. Another single-arm Phase 2 study (NCT01833572) showed that neoadjuvant gefitinib is a feasible treatment for patients with Stage II-IIIA NSCLC harboring EGFR mutations, with an ORR of 54.5%, a MPR rate of 24.2%, and a median DFS of 33.5 months. The EMERGING-CTONG 1103 trial was the first randomized Phase 2 study comparing neoadjuvant erlotinib with chemotherapy in patients with locally advanced (Stage IIIA-N2) NSCLC with EGFR-sensitive mutations. The final results, with a median follow-up of 62.5 months, showed that the PFS in the neoadjuvant erlotinib group was significantly longer than in the chemotherapy group, although this did not translate into an OS benefit. Preliminary results from ongoing clinical trials with osimertinib suggest that this third-generation EGFR-TKI is generally safe and may be an effective neoadjuvant treatment option. This study aims to investigate the efficacy and safety of neoadjuvant furmonertinib combined with anlotinib and chemotherapy in resectable stage II-III EGFR-mutant NSCLC.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
44
The enrolled patients are planned to receive preoperative treatment with a combination of furmonertinib and anrotinib, along with platinum-based doublet chemotherapy. Three weeks after the completion of this treatment, they will undergo curative lung lobe resection and systemic lymph node dissection. Postoperatively, they will continue taking furmonertinib for one year. In case of disease progression, they will be switched to comprehensive therapy.
Shanghai Pulmonary Hospital
Shanghai, Shanghai Municipality, China
Objective Response Rate
According to RECIST 1.1, objective response rate (ORR) refers to the proportion of patients whose tumors have shrunk to a certain extent and maintained that response for a specific duration, including those with complete response (CR) and partial response (PR). Complete response is defined as the complete disappearance of all target lesions, with the shortest diameter of any pathological lymph nodes (including both target and non-target nodes) shrinking to less than 10mm. Partial response is characterized by at least a 30% reduction in the diameter of the target lesion compared to baseline levels. In this study, ORR is defined as the proportion of patients who completed neoadjuvant therapy before surgery and achieved either CR or PR based on CT evaluation three weeks after treatment.
Time frame: 3 Weeks
Major Pathological Response
The Major Pathological Response (MPR) is defined as the proportion of patients, among all those who have completed treatment, with less than 10% residual primary tumor under microscopic examination with hematoxylin and eosin (HE) staining.
Time frame: 3 Weeks
Complete Pathological Response
Complete Pathological Response (CPR) is defined as the proportion of patients, among all those who have completed treatment, in whom there is no residual cancer in the primary tumor and lymph nodes under HE staining microscopy.
Time frame: 3 Weeks
R0 Resection Rate
The R0 resection rate is defined as the proportion of patients whose surgical margins are negative and there is no residual tissue visible under the microscope after the operation among all patients who have completed treatment.
Time frame: 3 Weeks
Disease Free Survival
The disease-free survival (DFS) refers to the time from curative surgery to the time when the patient experiences recurrence or death due to disease progression.
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Time frame: 5 years
Overall Survival
The overall survival (OS) is defined as the time from randomization to the occurrence of death from any cause in participants.
Time frame: 5 years
Treatment-Related Adverse Events
Treatment-related adverse events refer to the number of adverse events related to the neoadjuvant treatment regimen assessed according to CTCAE V4.0.
Time frame: 3 Months
Health-Related Quality of Life
The health-related quality of life (HRQOL) was evaluated according to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30 \& LC13, Version 3) for lung cancer patients.
Time frame: 5 years