Efficacy of antiangiogenic therapy in patients with advanced SMARCA4-deficient thoracic tumor

Abstract

Background

SMARCA4 (BRG1)-deficient thoracic tumors (SDTTs) are frequently diagnosed at an advanced stage and had poor prognosis, underscoring the critical importance of seeking out novel therapeutic avenues, particularly in the realm of antiangiogenic treatment. However, the efficacy of antiangiogenic therapy in SDTT remains unknown.

Method

We conducted a retrospective cohort study at SYSUCC from August 1, 2018, to August 15, 2024, screening patients diagnosed with advanced SDTTs confirmed by immunohistochemistry.

Results

A total of 151 patients with advanced SDTTs were enrolled in the study, including 49 patients received anti-angiogenic therapy and 102 patients never. The ORR and DCR of first-line therapy with antiangiogenic therapy was 51.4 % and 86.5 %, respectively, compared to only 37.1 % and 78.7 % for those without antiangiogenic therapy. The median PFS of SDTTs treated with antiangiogenic therapy was significantly longer than those without (7.97vs.5.87 months, HR [95 %CI]: 0.612[0.380–0.984], P = 0.043). For patients who did not receive immune checkpoint inhibitors (ICIs), the median PFS of SDTTs treated with anti-angiogenic agent combined with chemotherapy (C + A) was longer than those treated with chemotherapy alone (C) (5.10 vs 2.57 months, HR [95 %CI]: 0.365[0.137–0.968], P = 0.043). For patients received chemotherapy and ICIs, the addition of anti-angiogenic agent (C + I + A) provided significantly longer PFS (11.90 vs 6.90 months, HR [95 %CI]:0.425, [0.221–0.818], P = 0.010). This C + I + A therapy outperforms C + A therapy, showing the longest PFS (11.90 vs 5.10 months, HR [95 %CI]:0.294[0.112–0.772], P = 0.013).

Conclusion

The administration of antiangiogenic therapy shows a promising effect in first-line therapies for advanced SDTT patients. The C + I + A combination therapy is the optimal solution among currently available treatment options.