Adjuvant chemotherapy of three steps (ACTS) in patients with newly diagnosed advanced ovarian cancer: interim analysis of a randomized phase II trial

Abstract

<h3>Objectives:</h3> Decades ago, we developed adjuvant chemotherapy of three steps (ACTS) in advanced ovarian cancer, of which the first step is first-line platinum–taxane chemotherapy for six cycles, the second step is cyclophosphamide-etoposide per four weeks for six cycles, the third step is cyclophosphamide-platinum per eight weeks for six cycles. Here, we aimed investigate the efficacy and safety of ACTS in advanced ovarian cancer by randomized controlled trial. <h3>Methods:</h3> We conducted a randomized, open-label, controlled single center phase 2 trial. Eligible patients had newly diagnosed, advanced (FIGO2014 stage IIIc/IV), high-grade ovarian cancer and were having a complete response after optimal cytoreductory surgery and first-line platinum–taxane chemotherapy. Patients were randomly assigned in a 1:1 ratio to receive step 2 and 3 of ACTS (ACTS group, step 2: cyclophosphamide 0.4g d1-d3 IV + etoposide 0.1g d1-d3 IV per 4 weeks for six cycles; step 3: cyclophosphamide 0.6g d1-d2 IV + carboplatin AUC=5 d1 IV per 8 weeks for 6 cycles) or no treatment (control group). The primary endpoint was overall survival, the secondary endpoints were progression-free survival and safety. <h3>Results:</h3> Of the 130 patients who underwent randomization, 65 were assgined to ACTS group. In the interim analysis, the median progression-free survival was significantly longer in the ACTS group than in the control group (22.0 months vs. 9.53 months; hazard ratio for disease progression or death, 0.559; 95% confidence interval [CI], 0.368-0.849; P=0.006, Fig.1). In the interim analysis of overall survival (performed after the deaths of 15 of 130 patients [11.8%] in the overall population), the estimated Kaplan–Meier probability of survival at 36 months was 90.7% in the ACTS group and 79.0% in the control group (hazard ratio for death, 0.42; 95% CI, 0.146 to 1.21). The most common adverse events of grade 3 or higher were neutropenia (in 62.7%), and thrombocytopenia (in 11.9%). No treatment-related deaths occurred. <h3>Conclusions:</h3> Among patients with newly diagnosed advanced ovarian cancer who had a response to platinum-based chemotherapy, those who received adjuvant chemotherapy of three steps (ACTS) had significantly longer progression-free survival than those who didn't. (ClinicalTrials., NCT02562365.).