Clinical and molecular characterization of the vinorelbine-platinum chemotherapeutic regimen in HER2(-) metastatic breast cancer

IntroductionDespite rapidly improving therapeutics, challenges remain in 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 aim to investigate the clinical and molecular effects of vinorelbine-platinum in heavily pretreated HER2-negative mBC, as well as the role of addition of bevacizumab. Material and methodsWe 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. ResultsThe 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. ConclusionThe vinorelbine-platinum regimen, particularly with bevacizumab, shows 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.