Neoadjuvant anlotinib/sintilimab plus chemotherapy in triple-negative breast cancer (NeoSACT): Phase 2 trial

Tumor angiogenesis contributes to immune evasion, and vascular normalization enhances immunotherapy response by reshaping the tumor microenvironment. This phase 2 trial evaluates neoadjuvant anlotinib (antiangiogenic), sintilimab (programmed cell death protein 1 [PD-1] inhibitor), and chemotherapy in 29 patients with stage II-III triple-negative breast cancer (TNBC). The primary endpoint, pathological complete response (pCR), is achieved in 69.0% (95% confidence interval [CI]: 49.0%-85.0%), with an 86.2% minimal residual disease (residual cancer burden [RCB] 0 + 1) rate. Notably, programmed death-ligand 1 (PD-L1)-negative patients achieve a 75.0% pCR rate, comparable to PD-L1-positive patients (64.7%). The 2-year event-free survival (EFS) is 92.4%, with 100% EFS in pCR patients. Grade 3/4 adverse events occur in 31.0% of patients, primarily rash and hematologic toxicities. These results demonstrate that combining antiangiogenic therapy with immunotherapy and chemotherapy enhances treatment efficacy, potentially overcoming PD-L1 limitations, and supports further investigation in high-risk TNBC. This trial was registered at ClinicalTrials.gov (NCT04877821).