Abstract PO3-27-12: Dexamethasone is necessary for preventing acute emesis induced by anthracycline/cyclophosphamide chemotherapy (HELEN-009) : a multicenter, randomized, open-labeled phase 3 trial

Abstract

Abstract Background Olanzapine, in combination with NK1 receptor antagonist (RA), 5-hydroxytryptamine-3 (5-HT3) RA, and dexamethasone, is now the standard approach to prevent chemotherapy-induced nausea and vomiting (CINV). In this study, we assessed the preventive effect of removing dexamethasone from the quadruple standard antiemetic regimen on CINV caused by anthracycline/cyclophosphamide chemotherapy. Methods The HELEN-009 was a multicenter, randomized, open-labeled phase 3 trial to evaluate the efficacy of NK1RA,5-HT3RA and Olanzapine triplet-combination antiemetic therapy done in 3 hospitals in China.Key inclusion criteria were patients with early breast cancer who were scheduled to be treated with epirubicin plus cyclophosphamide chemotherapy for the first time, age between 18 and 75 years, and with Eastern Cooperative Oncology Group performance status of 0–1. Eligible patients were randomly assigned (1:1) to receive either fosaprepitant, tropisetron, dexamethasone and olanzapine(quadruple group)or fosaprepitant, tropisetron and olanzapine without dexamethasone(triple group). Patients were randomly assigned to interventions by use of a web entry system and the minimization method with a random component, with age as factors of allocation adjustment. The primary endpoint was the proportion of patients who achieved a complete response, defined as absence of vomiting and no use of rescue medications in the overall phase (days 1–5) after starting chemotherapy. All randomly assigned patients who satisfied eligibility criteria received epirubicin plus cyclophosphamide chemotherapy were included in efficacy analysis. All patients who received any treatment in this study were assessed for safety. This study is registered at Clinical Trials Registry, number NCT05242874. Findings Between January 2022 and July 2023, 439 patients with breast cancer were enrolled in the study, with 218 participants randomly assigned to quadruple group and 221 participants assigned to triple group. All eligible patients were observed 120 h after epirubicin plus cyclophosphamide chemotherapy initiation. One patient in the quadruple group withdrew consent. One patient in the quadruple group and one in triple group discontinued treatment on day 1 and was excluded from the efficacy analysis. In the overall phase, the proportion of patients who achieved a complete response was 180 (83.3% [95% CI 78.3–88.3] of 216 patients in the quadruple group and 137 (62.4% [55.8–68.7] of 220 patients in the triple group (p< 0·0001). No grade 3 or higher treatment-related adverse events occurred in either of the groups. Interpretation Dexamethasone remains essential in preventing acute emesis in patients receiving epirubicin plus cyclophosphamide chemotherapy. Table. Proportion of patients in the efficacy analysis set achieving a complete response Table. Treatment-related adverse events with an incidence ≥ 2% Citation Format: Xiuchun Chen, Jiao Dechuang, Chongjian Zhang, Xianfu Sun, Zhenduo Lu, Lianfang Li, Jianghua Qiao, Chengzheng Wang, Min Yan, Yueqing Feng, Ya Wei, Zhenzhen Liu. Dexamethasone is necessary for preventing acute emesis induced by anthracycline/cyclophosphamide chemotherapy (HELEN-009) : a multicenter, randomized, open-labeled phase 3 trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-27-12.