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Efficacy of antiangiogenic therapy in patients with advanced SMARCA4-deficient thoracic tumor
Mengting Shi1, Xueyuan Chen2, Ting Lin3
1Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, No. 7 Raoping Road, Shantou, Guangdong 515000, China; Shantou University Medical College, 22 Xinling Road, Shantou, Guangdong 515000, China; Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
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.
Insights
Antiangiogenic therapy shows promise for advanced SMARCA4-deficient thoracic tumors (SDTTs). Combination therapy including chemotherapy, antiangiogenic agents, and immune checkpoint inhibitors (ICI) offers the longest progression-free survival.
Area of Science:
- Oncology
- Thoracic Oncology
- Cancer Therapeutics
Background:
- SMARCA4-deficient thoracic tumors (SDTTs) often present at advanced stages with poor prognosis.
- Novel therapeutic strategies, especially antiangiogenic treatments, are crucial for improving outcomes in SDTT patients.
- The efficacy of antiangiogenic therapy in SDTTs has not been previously established.
Purpose of the Study:
- To evaluate the efficacy of antiangiogenic therapy as a first-line treatment for advanced SDTTs.
- To compare treatment outcomes between SDTT patients receiving antiangiogenic therapy and those who did not.
- To identify the optimal combination therapy for advanced SDTTs.
Main Methods:
- A retrospective cohort study was conducted involving 151 patients with advanced SDTTs.
- Patients were diagnosed via immunohistochemistry and treated between August 2018 and August 2024.
- Outcomes were compared between patients who received antiangiogenic therapy (n=49) and those who did not (n=102).
Main Results:
- Antiangiogenic therapy significantly improved objective response rate (ORR) and disease control rate (DCR) compared to no antiangiogenic therapy.
- Median progression-free survival (PFS) was longer in patients receiving antiangiogenic therapy (7.97 months vs. 5.87 months).
- Combination therapy with chemotherapy, antiangiogenic agents, and ICIs (C+I+A) demonstrated the longest PFS (11.90 months) compared to chemotherapy plus antiangiogenic therapy (C+A) or chemotherapy alone (C).
Conclusions:
- Antiangiogenic therapy demonstrates a promising effect in first-line treatment for advanced SDTT patients.
- The combination of chemotherapy, antiangiogenic agents, and immune checkpoint inhibitors (C+I+A) represents the optimal therapeutic strategy currently available for advanced SDTTs.
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