Bevacizumab, tislelizumab and nab-paclitaxel for previously untreated metastatic triple-negative breast cancer: a phase II trial.

BACKGROUND

Optimal first-line therapy for metastatic triple-negative breast cancer (mTNBC) varied in different situations. This phase II trial explores the efficacy and safety of combination regimens with vacizumab, slelizumab and b-paclitaxel (BETINA) in first-line setting for mTNBC.

METHODS

Patients with previously untreated advanced TNBC received tislelizumab 200 mg and bevacizumab on day 1 and nab-paclitaxel 125 mg/m on day 1, day 8 in 3-week cycles. Patients were randomized to bevacizumab 7.5 mg/kg or 15 mg/kg. The primary endpoint was investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors V.1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. The trial was registered at the Chinese Clinical Trial Registry (No. ChiCTR2200058567).

RESULTS

30 female patients were enrolled from March 11, 2021 to February 5, 2024. Nine patients receiving bevacizumab 15 mg/kg experienced significantly higher hypertension rates versus 7.5 mg/kg (55.5% vs 0%), prompting subsequent enrollment of 12 additional patients at 7.5 mg/kg. By November 30, 2024, the ORR was 73.3% and the disease control rate was 90.0%, while the median PFS was 6.0 months and the median OS was 19.8 months. No new safety signal was reported. Common treatment-related adverse events (AEs) included peripheral sensory neuropathy (83.3%), dyspepsia (70.0%), anemia (70.0%), leukocytopenia (66.7%), and pruritus (53.3%). Hypothyroidism (30.0%) was the most frequent immune-related AE. Biomarker analysis indicated that lower baseline interleukin (IL)-1α was associated with poor survival, while IL-2, vascular endothelial growth factor-A and insulin-like growth factor binding protein-7 levels significantly decreased at progression. RNA sequencing highlighted the enrichment of the fatty acid metabolism pathway in poor responders.

CONCLUSIONS

BETINA study demonstrated promising efficacy and favorable tolerance in treating patients with mTNBC with bevacizumab with tislelizumab and nab-paclitaxel.