A randomized, double-blind, placebo-controlled phase II study of olanzapine-based prophylactic antiemetic therapy for delayed and persistent nausea and vomiting in patients with HER2-positive or HER2-low breast cancer treated with trastuzumab deruxtecan: ERICA study (WJOG14320B).

We evaluated the efficacy of an olanzapine-based triplet regimen for preventing nausea and vomiting in patients receiving their first cycle T-DXd.

我们评估了基于奥氮平的三联方案在预防首次接受T-DXd治疗患者恶心和呕吐方面的疗效。

patients_and_methods

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.

这项多机构、随机、双盲、安慰剂对照（ERICA）II期研究招募了接受T-DXd第一周期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。

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.

患者从第1天至第6天被随机分配至每天一次口服5毫克奥氮平或安慰剂（1:1比率），并在第1天使用5-羟色胺受体拮抗剂和静脉注射6.6毫克或口服8毫克地塞米松。

The total observation period was 504 h (21 days) from the first T-DXd administration.

从首次T-DXd给药开始，总观察期为504小时（21天）。

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.

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救援药物，比较的一型错误率为0.2（单侧）。

Secondary endpoints included no nausea rate in the delayed and persistent phases (120-504 h), adverse eventby Common Terminology Criteria for Adverse Events (CTCAE) and patient-reported outcomes version of the CTCAE (PRO-CTCAE).

次要终点包括延迟和持续阶段（120-504小时）无恶心发生率、使用不良事件通用术语标准（CTCAE）和患者报告结果版CTCAE（PRO-CTCAE）的不良事件。

Results

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.

共有168名患者在日本的43个地点（2021年11月至2023年9月）被纳入研究，其中162名患者（奥氮平组，n=80；安慰剂组，n=82）被纳入符合方案集。

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).

主要终点得到满足，因为延迟阶段的完全缓解（CR）率在使用奥氮平的患者中显著高于安慰剂组（70.0%对比56.1%，P=0.047）。

Efficacy was maintained in the persistent phase (63.9% versus 44.4%).

在持续阶段，疗效得以维持（63.9%对比44.4%）。

No nausea rate was also greater with olanzapine (delayed phase: 57.5% versus 37.8%; persistent phase: 51.4% versus 31.9%).

使用奥氮平的无恶心率也更高（延迟期：57.5%对比37.8%；持续期：51.4%对比31.9%）。

CR rates in the delayed phase favored olanzapine across subgroups.

延迟期的完全缓解（CR）率在各个亚组中均倾向于奥氮平。

Appetite loss was also decreased with olanzapine.

食欲减退也随着奥氮平的使用而减少。

Hyperglycemia and somnolence were mostly of low-grade severity.

高血糖和嗜睡大多为低度严重。

Conclusions

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.

对于接受T-DXd治疗的患者，5毫克奥氮平连续使用6天，联合5-羟色胺3受体拮抗剂和地塞米松，似乎能有效预防延迟和持续的恶心和呕吐。