A retrospective study of the efficacy and safety of immune checkpoint inhibitors combined with chemotherapy for the treatment of SMARCA4-deficient thoracic tumors.

Abstract

Background: Thoracic tumors characterized by a deficiency in SMARCA4 are highly aggressive and linked to a poor prognosis. This retrospective study explores the efficacy and safety of immune checkpoint inhibitors (ICIs) in combination with chemotherapy for SMARCA4-deficient undifferentiated tumors (SMARCA4-dUT) and SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC).

Methods: A cohort of 59 individuals was analyzed, including 35 patients with SMARCA4-dUT and 24 with SMARCA4-dNSCLC.

Results: Clinical characteristics as gender, age, smoking status, and metastatic sites did not significantly vary between SMARCA4-dUT and SMARCA4-dNSCLC. Nonsense and frameshift mutations in the SMARCA4 gene can result in the loss of its protein expression. Following a median follow-up of 7.6 months, the median progression-free survival (mPFS) notably increased with ICIs-based combination therapy compared to chemotherapy, the mPFS was 12.60 vs. 4.03 months in the SMARCA4-dUT subgroup (P=0.007) and not reached vs. 3.42 months in the SMARCA4-dNSCLC subgroup (P=0.03). In stage IV patients, the risk of disease progression and death decreased with ICIs-based combination therapy vs. chemotherapy [ICIs-based therapy vs. chemotherapy: hazard ratio (HR) =0.076; 95% confidence interval (CI): 0.009-0.624]. The most prevalent grade 3 or higher adverse events (AEs) in both groups were hematologic decreases, consistent with typical chemotherapy AEs. No treatment-related AEs led to patient fatalities.

Conclusions: The combination of ICIs and chemotherapy is more effective than chemotherapy for patients with advanced SMARCA4-deficient thoracic tumors (SMARCA4-dTT), and the safety is manageable.