The cornerstone of luminal breast tumors treatment both in early and advanced settings is endocrine therapy (ET). Although extended adjuvant ET has demonstrated benefit, a significant percentage of patients relapse. In previous studies, the combination of ET with CDK4/6 inhibitors has shown unprecedented efficacy suggesting that inhibition of the cell cycle in combination with ET is a strategy to keep exploring. The efficacy and safety of metronomic VNB have been confirmed in preclinical and clinical studies and it is now considered a multi-mechanisms of action therapy that could offer advantages when combined with other drugs. VENTANA study is a “window-of-opportunity” trial designed to explore whether, similarly to CDK4/6 inhibitors, oral metronomic VNB in combination with endocrine therapy induces a superior antiproliferative effect than ET alone. We hypothesize that the synergistic biological effect of the combined treatment could be an alternative to CDK4/6 inhibitors in the treatment of luminal breast cancer patients.
Pts are randomized (1:1:1) to receive LET 2.5mg daily, oral VNB 50mg 3 days a week, or the combination. After 3 weeks of treatment, pts undergo surgery. Pre- and post-treatment (surgical) samples will be analyzed for gene expression. The primary objective is to test if oral metronomic VNB and LET induce a superior anti-proliferative effect than either drug alone in pts with early BC defined as Luminal by PAM50. This will be evaluated by the expression of 11 proliferative genes contained in the PAM50 subtype predictor (BIRC5, CCNB1, CDC20, CDCA1, CEP55, KNTC2, MKI67, PTTG1, RRM2, TYMS and UBE2C) as surrogate signature biomarker of its anticancer activity. In addition, 560 BC-related gene signatures will also be analyzed. Enrollment started in July 2016 in 10 sites across Spain. To date, 47 patients have been included. We expect to report full study results by Spring 2018.
Clinical trial identification
Legal entity responsible for the study
SOLTI Breast Cancer Research Group
All authors have declared no conflicts of interest.