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.