Furmonertinib Plus Radiotherapy for EGFR+ NSCLC With Pleural Effusion

Prior treatment

• Pre-existing interstitial lung disease (ILD) or infectious fever prior to treatment.
• Radiographic progression (PD) after 8-10 weeks of TKI therapy, or development of grade ≥ 2 ILD.
• Concurrent autoimmune disease requiring long-term oral corticosteroid therapy.
• Significant respiratory symptoms (e.g., chest tightness, cough) that preclude tolerance to radiotherapy.
• Active hepatitis B or C virus infection with concomitant grade \> 2 hepatic impairment. Patients may be considered eligible if liver function recovers to grade 1 after active hepatoprotective therapy and antiviral treatment.
• Poorly controlled or continuously progressive pleural effusion after 8-10 weeks of furmonertinib therapy.

Other illness

• Known hypersensitivity to furmonertinib.

Other

• Severe anemia.
• Symptomatic brain metastases.

• Age ≥ 18 years.
• Histologically or cytologically confirmed advanced lung adenocarcinoma.
• Unlimited number of metastatic lesions, but with involvement of no more than 3 organs.
• Previously untreated, clinical stage IV disease per AJCC/UICC 9th edition.
• Presence of pleural effusion as indicated by chest CT or ultrasound; cytological confirmation of malignant cells in the pleural effusion is preferred. If malignant cells are not detected in the pleural effusion, chest CT with contrast or whole-body PET/CT must demonstrate unequivocal pleural nodular metastases.
• After 8-10 weeks of furmonertinib therapy with or without therapeutic thoracentesis, the overall radiographic response is assessed as effective (CR + PR + SD), and malignant pleural effusion is adequately controlled (defined as no pleural effusion or only minimal pleural effusion on ultrasound or chest CT: maximum depth \< 3 cm, estimated volume \< 500 mL). Concurrent minimal pericardial effusion is permissible (defined as maximum diastolic width \< 1 cm on echocardiography, estimated volume \< 100 mL).
• No prior thoracic radiotherapy.
• Positive for EGFR-sensitive mutations (exon 19 deletion or exon 21 L858R).
• No prior systemic anticancer therapy.
• ECOG performance status 0-2, with a life expectancy of ≥ 12 weeks.
• At least one measurable lesion per RECIST 1.1.
• Adequate bone marrow function to tolerate anticancer treatment: WBC ≥ 3 × 10⁹/L, Hb ≥ 80 g/L, PLT ≥ 75 × 10⁹/L, and absolute neutrophil count (NEUT) ≥ 1.5 × 10⁹/L.
• Essentially normal hepatic and renal function:
  • Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance (CrCl) ≥ 50 mL/min;
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN (≤ 5 × ULN is acceptable in patients with liver metastases);
  • Total bilirubin (TBIL) ≤ 1.5 × ULN;
  • Albumin ≥ 30 g/L and prealbumin ≥ 150 g/L.
• Asymptomatic brain metastases.
• Written informed consent obtained from all subjects.