Addition of Bevacizumab to Vinorelbine-Platinum combination is efficacious in Heavily Pretreated HER2-Negative Metastatic Breast Cancer.

Despite rapidly improving therapeutics, challenges remain in the treatment of advanced breast cancer. Vinorelbine, a semisynthetic vinca alkaloid, is effective and well-tolerated in breast cancer treatment. The combination of vinorelbine and platinum-combination is a well-tolerated but underreported chemotherapy regimen. Bevacizumab, a VEGF-neutralizing antibody, has shown efficacy in HER2-negative metastatic breast cancer (mBC) when combined with chemotherapy. In this study we aimed to investigate the clinical and molecular effects of vinorelbine-platinum in heavily pretreated HER2-negative mBC, as well as the impact of adding bevacizumab. We conducted a retrospective study at Taipei Veterans General Hospital to evaluate the effectiveness of the vinorelbine-platinum regimen in heavily pretreated HER2-negative mBC patients from 2016 to 2020, with a portion of patients receiving additional bevacizumab. To model the molecular perturbations at a cellular level, transcriptional profiling of a triple negative breast cancer cell line treated with cisplatin-vinorelbine was done by RNA-sequencing. The cohort included 54 patients. 50% of the patients received ≥ 5 lines of systemic treatment in the metastatic setting. All the patients had received anthracyclines and taxane. In patients treated with vinorelbine-platinum combination, the median progression-free survival (PFS) and overall survival (OS) were 2.3 and 7.3 months, respectively. With bevacizumab, median PFS improved to 4.1 months. Objective response rate (ORR) and disease control rate (DCR) without bevacizumab were 11.1% and 27.7%, respectively, improving to 25% and 83.3% with bevacizumab. Adverse events occurred in 37.0% of patients, with no grade IV events reported. Transcriptional profiling revealed significant downregulation of MAPK pathway, angiogenesis, and growth factor signaling related genes. The vinorelbine-platinum regimen, particularly with bevacizumab, shows potential efficacy even in heavily pretreated HER2-negative metastatic breast cancer patients. Molecular analyses of treated cells highlight potential targets and mechanisms of action, providing a basis for future therapeutic strategies.