To explore the efficacy and safety of neoadjuvant furmonertinib combined with bevacizumab in the treatment of resectable and potentially resectable stage III-IVA EGFR mutation-positive lung adenocarcinoma.

The best treatment for lung cancer is still radical resection, which is indicated for stage I-II and some stage III patients, but surgery is only suitable for 20-25% of NSCLC patients. Furmonertinib is a third-generation TKI drug. Compared with first and second-generation TKI drugs, it has good benefits in the Chinese population, patients with brain metastases, and patients with 19del/L858R mutation, with better and longer-lasting effects, and can significantly improve the progression-free survival of patients. Neoadjuvant therapy can shrink the tumor, increase the rate of complete surgical resection, remove micrometastases, and reduce the risk of recurrence. Cases of patients with locally advanced (IIIA-N2) NSCLC have been reported with neoadjuvant TKI therapy, and it has been found that neoadjuvant TKI therapy can downgrade or even complete tumor remission. However, for locally advanced potentially resectable, or EGFR mutation-positive NSCLC patients with single-organ metastasis, the efficacy of third-generation EGFR-TKI combined with VEFGR inhibitor combined with targeted therapy after induction and surgery is still unclear. Limited clinical research data suggest that this new treatment mode (induction therapy-surgery-adjuvant therapy) can significantly improve the progression-free survival of patients. However, the overall survival rate under the new treatment mode and the promotion of clinical work urgently need higher-level clinical evidence to support clinical decision-making.

Inclusion Criteria:

• Lung adenocarcinoma patient with EGFR sensitive mutation as confirmed by needle biopsy;
• At stage III-IVA (TNM Staging, Version 8) as identified by chest CT, PET-CT or/and EBUS;
• No systemic metastasis (confirmed by head MRI, whole body bone scan, PET-CT, liver and adrenal CT, etc.);
• With the feasiblility or potential feasibility to receive radical surgery (radical lung lobectomy+systematic lymph node dissection);
• Good lung function that could tolerate surgical treatment;
• Aged >= 18 years;
• At least one measurable tumor foci (the longest diameter measured by CT shall be > 10 mm);
• Other major organs shall function well (liver, kidney, blood system, etc.):
• ECOG PS score shall be 0-1;
• The child-bearing female must undergo pregnancy test within 7 days before starting the treatment and the result shall be negative. Reliable contraceptive measures, such as intrauterine device, contraceptive pill and condom, shall be adopted during the trial and within 30 days after completion of the trial. The child-bearing male shall use condom for contraception during the trial and within 30 days after completion of the trial;
• The patient shall sign the Informed Consent Form.

Exclusion Criteria:

• The patient has undergone any systemic anti-cancer treatment for NSCLC, including cytotoxic drug treatment, targeted drug treatment and experimental treatment, etc.;
• The patient suffers from any unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina pectoris, angina pectoris that starts to attack within the last 3 months, congestive heart failure [≥ Grade II specified by New York Heart Association (NYHA)], cardiac infarction (6 months before enrollment), severe arrhythmia and liver, kidney or metabolic diseases that requires drug treatment;
• The patient is a carrier of HIV;
• The patient is currently suffering from interstitial lung disease;
• The patient had undergone other major systemic operations or suffered from severe trauma within 3 months before the trial;
• The patient is allergic to furmonertinib or its any excipients;
• The patient is allergic to bevacizumab or its any excipients;
• The female patient is in pregnancy or lactation period;
• There are any conditions under which the investigator considers the patient is not suitable to be enrolled.