Efficacy and Safety Analysis of First-Line ABCP Therapy in Advanced SMARCA4-Mutated NSCLC

SMARCA4 mutation is clinically known to be an independent poor prognostic factor. Both TCGA and the investigators institution's preliminary research indicate that the median overall survival (OS) of mutated patients is significantly shorter than that of wild-type patients (32 months vs. 157.7 months, respectively, P=0.001); it is associated with chemotherapy/immunotherapy resistance, rapid progression, and poor prognosis (OS\<12 months). Current standard first-line treatments (such as platinum-based chemotherapy ± immunotherapy) have limited efficacy in SMARCA4-mutated patients (ORR\<30%, PFS\<4 months). Additionally, NapsinA-positive expression can improve the survival of mutated patients (median OS: 32 months vs. 15 months, P=0.033), but this effect exists only in the SMARCA4-mutated group. The ABCP regimen has a synergistic mechanism: Atezolizumab (anti-PD-L1): reverses the immunosuppressive microenvironment; Bevacizumab (anti-VEGF): inhibits angiogenesis and enhances T-cell infiltration; Platinum + Paclitaxel: directly kill tumor cells and release neoantigens. Therefore, the investigators preset that SMARCA4 mutation may affect chemotherapy/immunotherapy response through epigenetic regulation, and its value as a predictive biomarker needs to be validated. Hence, the purpose of this study is to observe and explore the efficacy and safety of first-line ABCP four-drug combination therapy in patients with advanced SMARCA4-mutated non-small cell lung cancer.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

1. Patients with pathologically confirmed NSCLC, meeting the following criteria based on the IASLC 9th Edition Lung Cancer TNM Staging System (International Association for the Study of Lung Cancer/Union for International Cancer Control): Histologically or cytologically confirmed unresectable locally advanced (Stage IIIB/IIIC) disease not amenable to curative-intent concurrent chemoradiotherapy, metastatic, or recurrent (Stage IV) non-squamous NSCLC;
2. Confirmed SMARCA4 mutation (verified by NGS testing);
3. ECOG performance status 0-1, with no prior systemic anticancer therapy;
4. Absence of driver gene mutations (e.g., EGFR, ALK, ROS1);
5. Patients capable of providing sufficient blood samples (detailed in sample requirements) and complete baseline clinical data, including: age, gender, smoking history, family history, lesion location(s), lesion size(s), number of lesions, tumor markers, pathological indicators, treatment records, and re-examination/follow-up information;
6. Voluntary participation with signed informed consent form, willingness to undergo follow-up assessments and provide treatment process details, efficacy data, and prognostic information, with commitment to complete the entire study.

Exclusion Criteria:

* (1) Active autoimmune diseases or interstitial lung disease; (2) Bleeding tendency or contraindications to Bevacizumab.