Results of the prospective randomized controlled trial VOG-01: Neoadjuvant endocrine therapy ribociclib + fulvestrant + GnRH-a versus chemotherapy 4 AC + 4 T for early HR+/HER2-negative breast cancer in premenopausal patients.

606 Background: CDK4/6 inhibitors are used to treat HR+/HER2- metastatic breast cancer in combination with endocrine therapy. However, there is still a lack of evidence about combined endocrine therapy in neoadjuvant setting. VOG-01 is a phase II randomized trial that evaluated the effects of combination ribociclib plus fulvestrant and GnRH-a as neoadjuvant therapy in premenopausal patients. Methods: Premenopausal women with HR+/HER2-negative stage II-III were randomly assigned to Fulvestrant (500 mg on the 1st, 15th, 28th days of the first cycle, then once every 28 days), Triptorelin (3.75 mg every 28 days) and Ribociclib (600 mg daily, 3 weeks/4) during 16-24 weeks (NET), or Doxorubicin 60 mg/m2 + Cyclophosphamide 600 mg/m2 x4 21-day courses followed by Docetaxel 75 mg/m2 x4 21-day courses (NCT). Primary endpoint was objective response rate. Secondary endpoints were pathological response rate (RCB), frequency of breast-conserving surgery, severity of adverse events and the quality of life (EORTC QLQ-C30). Results: Eighty two patients were recruited. The objective response rate was 83% in the NET and 71% in the NCT (p = 0.2). Complete pathological response (RCB 0) was in 2 cases (5%) in the NET and in 4 cases (10%) in the NCT; RCB I was in 1 case (2.6%) in the NCT and did not occur in the NET; RCB II - 55% in the NET and 62% in the NCT, RCB III was in 40% and 26% respectively. Breast-conserving surgery were not so common in both groups: 37% in the NET and 32% in the NCT (p=0.5). Severe adverse events (CTCAE ver 5 G3-4) were 66% in the NET and 87% in NCT (p < 0.019). Quality of life significantly decreased during NCT compared with NET: the total score was 75.7±22.2, 42.0±19.7, 66.3±12.9 in NCT at visits on 1-12-24- weeks and 76.4±20, 70.7±25.4, 76.1±20.5 in NET at the same visits (p < 0.05). Conclusions: For the first time randomised trial comparing NET and NCT was conducted in premenopausal women with HR+/HER2- early breast cancer. NET was not inferior to standard NCT in terms of objective response rate, complete or pronounced pathological response rate and breast-conserving surgery. At the same time it was associated with a lower severity of adverse events and increased quality of life. Nevertheless new treatment approach requires confirmation of its effectiveness in large studies. Clinical trial information: NCT04753177 .