Clinical responses and drug safety of immunotherapy combined with chemotherapeutic regime at first-line in advanced SMARCA4-deficient non-small cell lung cancer: a real-world retrospective study

Non-Small cell lung cancer (NSCLC) characterized by SWI/SNF (SWItch/Sucrose Non-Fermentable)-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4) deficiency is highly invasive and have poor prognosis, but there is still no clear conclusion on whether immunotherapy has therapeutic effects in the absence of targeted drugs. Here, we retrospectively collected 71 participants with SMARCA4 deficient non-small cell lung cancer, and analyzed their clinical characteristics and long-term survival status. Univariate analysis on PFS was performed to further explicit candidate indicators to evaluate its safety and adverse events. SMARCA4-deficient NSCLC predominantly affects middle-aged to elderly male smokers. Most patients are diagnosed at stage IIIB-IV, resulting in ineligibility for surgical intervention. Histologically, adenocarcinoma is the most frequent subtype, followed by undifferentiated carcinoma; these tumors are typically poorly differentiated and exhibit high proliferation indices. There are significant differences in the impact of smoking history, smoking index, tumor distribution type, tumor stage, and Programmed death-ligand 1 (PD-L1) expression on the overall survival of SMARCA4 deficient NSCLC. Compared with chemotherapy-based treatment, chemotherapy combined with immunotherapy significantly prolongs the median overall survival (mOS) by 23.00 months ( P = 0.023). The most common adverse events in the two treatment groups were hematological (17/16 cases in CT/CTIO group, respectively, P = 0.942) and hepatic dysfunction (16/15 cases in CT/CTIO group, respectively, P = 0.954) with no obvious differences. Combinational therapeutic regime on immunotherapy with chemotherapy may reach to embraced clinical outcomes among advanced SMARCA4-deficient NSCLC cohort with favorable safety profiles in a real-world setting, featuring an extended median overall survival compared to those receiving chemotherapy alone.