Sakai H, Tsurutani J, Ozaki Y, Ishiguro H, Nozawa K, Yamanaka T, Aogi K, Matsumoto K, Iwasa T, Tokiwa M, Tsuneizumi M, Miyoshi Y, Kitagawa C, Yamamoto M, Takano Y, Imamura C K, Chiba Y, Takiguchi D, Ezumi T, Takano T
Advanced Cancer Translational Research Institute, Showa University, Tokyo.
Advanced Cancer Translational Research Institute, Showa University, Tokyo.
Ann Oncol. 2025 Jan;36(1):31-42. doi: 10.1016/j.annonc.2024.09.001. Epub 2024 Sep 14.
Nausea and vomiting are common adverse events associated with trastuzumab deruxtecan (T-DXd). We evaluated the efficacy of an olanzapine-based triplet regimen for preventing nausea and vomiting in patients receiving their first cycle T-DXd.
This multi-institutional, randomized, double-blind, placebo-controlled (ERICA) phase II study enrolled patients with human epidermal growth factor receptor 2-positive/human epidermal growth factor receptor 2-low metastatic breast cancer receiving their first cycle of T-DXd. Patients were randomized to olanzapine 5 mg or placebo once daily (1 : 1 ratio) from day 1 to day 6, plus a 5-hydroxytryptamine type 3 receptor antagonist and dexamethasone 6.6 mg intravenously or 8 mg orally on day 1. The total observation period was 504 h (21 days) from the first T-DXd administration. The primary endpoint was complete response (CR), defined as no emetic events and no rescue medications, in the delayed phase (24-120 h after T-DXd), with the type I error rate of 0.2 (one-sided) for the comparison. Secondary endpoints included no nausea rate in the delayed and persistent phases (120-504 h), adverse event by Common Terminology Criteria for Adverse Events (CTCAE) and patient-reported outcomes version of the CTCAE (PRO-CTCAE).
In total, 168 patients were enrolled at 43 sites in Japan (November 2021-September 2023) with 162 patients (olanzapine, n = 80; placebo, n = 82) included in the per protocol set. The primary endpoint was met as the delayed phase CR rate was significantly greater with olanzapine than placebo (70.0% versus 56.1%, P = 0.047). Efficacy was maintained in the persistent phase (63.9% versus 44.4%). No nausea rate was also greater with olanzapine (delayed phase: 57.5% versus 37.8%; persistent phase: 51.4% versus 31.9%). CR rates in the delayed phase favored olanzapine across subgroups. Appetite loss was also decreased with olanzapine. Hyperglycemia and somnolence were mostly of low-grade severity.
Olanzapine 5 mg for 6 days with 5-hydroxytryptamine type 3 receptor antagonist and dexamethasone appears effective for T-DXd-treated patients to prevent delayed and persistent nausea and vomiting.
恶心和呕吐是与曲妥珠单抗德鲁替康（T-DXd）相关的常见不良事件。我们评估了基于奥氮平的三联方案对接受首个周期T-DXd治疗的患者预防恶心和呕吐的疗效。
这项多中心、随机、双盲、安慰剂对照（ERICA）II期研究纳入了接受首个周期T-DXd治疗的人表皮生长因子受体2阳性/人表皮生长因子受体2低表达转移性乳腺癌患者。患者从第1天到第6天被随机分为每日一次口服5毫克奥氮平或安慰剂（1:1比例），并在第1天静脉注射5-羟色胺3型受体拮抗剂和6.6毫克地塞米松或口服8毫克地塞米松。从首次给予T-DXd开始的总观察期为504小时（21天）。主要终点是延迟期（T-DXd给药后24 - 120小时）的完全缓解（CR），定义为无呕吐事件且无需使用解救药物，比较的I类错误率为0.2（单侧）。次要终点包括延迟期和持续期（120 - 504小时）的无恶心率、根据不良事件通用术语标准（CTCAE）的不良事件以及CTCAE患者报告结局版本（PRO-CTCAE）。
在日本的43个地点共纳入了168例患者（2021年11月 - 2023年9月），符合方案集纳入了162例患者（奥氮平组，n = 80；安慰剂组，n = 82）。奥氮平组延迟期CR率显著高于安慰剂组（70.0%对56.1%，P = 0.047），达到了主要终点。在持续期疗效得以维持（63.9%对44.4%）。奥氮平组的无恶心率也更高（延迟期：57.5%对37.8%；持续期：51.4%对31.9%）。延迟期CR率在各亚组中均有利于奥氮平。奥氮平还可减轻食欲减退。高血糖和嗜睡大多为低级别严重程度。
5毫克奥氮平连用6天联合5-羟色胺3型受体拮抗剂和地塞米松对接受T-DXd治疗的患者预防延迟性和持续性恶心及呕吐似乎有效。
