Furmonertinib Plus Radiotherapy for EGFR+ NSCLC With Pleural Effusion

This study is designed as a prospective, multi-center investigation to explore the efficacy and safety of furmonertinib combined with upfront thoracic radiotherapy with or without metastatic lesion radiotherapy in subjects with EGFR-mutant NSCLC and malignant pleural effusion (MPE), aiming to provide additional evidence-based medical support for optimizing the management of NSCLC-MPE subjects. In addition, peripheral blood ctDNA next-generation sequencing (NGS) will be performed at two time points-before the first furmonertinib treatment and one month after the completion of thoracic radiotherapy-to identify subpopulations most likely to benefit from this therapeutic approach and to elucidate resistance mechanisms specific to the radiotherapy-plus-furmonertinib combination, ultimately facilitating more personalized care for these subjects.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

1. Age ≥ 18 years.
2. Histologically or cytologically confirmed advanced lung adenocarcinoma.
3. Unlimited number of metastatic lesions, but with involvement of no more than 3 organs.
4. Previously untreated, clinical stage IV disease per AJCC/UICC 9th edition.
5. 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.
6. 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).
7. No prior thoracic radiotherapy.
8. Positive for EGFR-sensitive mutations (exon 19 deletion or exon 21 L858R).
9. No prior systemic anticancer therapy.
10. ECOG performance status 0-2, with a life expectancy of ≥ 12 weeks.
11. At least one measurable lesion per RECIST 1.1.
12. 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.
13. Essentially normal hepatic and renal function:

    1. Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance (CrCl) ≥ 50 mL/min;
    2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN (≤ 5 × ULN is acceptable in patients with liver metastases);
    3. Total bilirubin (TBIL) ≤ 1.5 × ULN;
    4. Albumin ≥ 30 g/L and prealbumin ≥ 150 g/L.
14. Asymptomatic brain metastases.
15. Written informed consent obtained from all subjects.

Exclusion Criteria:

1. Pre-existing interstitial lung disease (ILD) or infectious fever prior to treatment.
2. Radiographic progression (PD) after 8-10 weeks of TKI therapy, or development of grade ≥ 2 ILD.
3. Concurrent autoimmune disease requiring long-term oral corticosteroid therapy.
4. Severe anemia.
5. Known hypersensitivity to furmonertinib.
6. Significant respiratory symptoms (e.g., chest tightness, cough) that preclude tolerance to radiotherapy.
7. 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.
8. Poorly controlled or continuously progressive pleural effusion after 8-10 weeks of furmonertinib therapy.
9. Symptomatic brain metastases.

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