Opinion: Addition of Olanzapine Effectively Manages Nausea During T-DXd Treatment

Olanzapine may be effective in curbing nausea in patients undergoing treatment with T-DXd.

Trastuzumab deruxtecan (T-DXd; Enhertu) is an antibody-drug conjugate used as standard therapy for HER2-positive and HER2-low unresectable or metastatic breast cancer.¹ It is classified by the National Comprehensive Cancer Network (NCCN) as having high emetogenic risk.²

Managing nausea in these patients can be challenging for oncology nurses due to the wide variety of available antiemetics, potential drug-drug interactions, and a patient’s prior success or failure with certain antiemetics, among other factors. Establishing protocols for managing side effects in specific treatment regimens is essential for streamlining care, improving patient tolerance, and reducing treatment interruptions or discontinuations.

Olanzapine has shown effectiveness in relieving chemotherapy-induced nausea and vomiting, particularly when combined with 5-HT3 receptor antagonists (5-HT3RAs), such as ondansetron or palonosetron, which block serotonin receptors to reduce nausea, and dexamethasone. A recent study by Sakai et al. aimed to assess the superiority of olanzapine over placebo for managing delayed and persistent nausea in patients receiving T-DXd.¹

The ERICA study: Evaluating Nausea Management with Olanzapine

The ERICA study was a placebo-controlled, double-blind, randomized phase II trial conducted in 43 hospitals in Japan between November 2021 and September 2023. Eligible patients were adults with HER2-positive or HER2-low metastatic breast cancer who were receiving their first cycle of T-DXd. Key exclusion criteria included patients requiring antiemetic treatment for nausea and vomiting at the time of enrollment.

Participants were randomized in a 1:1 ratio to receive either olanzapine (5 mg daily) or placebo from days 1 to 6, along with a 5-HT3RA (such as palonosetron) and dexamethasone on day 1. The primary endpoint was the complete response (CR) rate during the period of 1-5 days post-T-DXd, known as the delayed phase, defined as no emetic episodes and no use of rescue medication. Secondary endpoints included complete response (CR) rates during the acute phase (the first 24 hours following treatment), the persistent phase (days 2 to 6 after treatment), and the overall phase (encompassing both acute and persistent phases), as well as nausea severity and other symptoms, which were recorded daily in an electronic symptom diary.

Between November 2021 and September 2023, 168 patients were enrolled and randomly assigned to receive olanzapine (n = 85) or placebo (n = 83). After accounting for withdrawals and exclusions, the full analysis set included 165 patients (olanzapine, n = 82; placebo, n = 83).

Complete response (CR) rates during the delayed phase, was significantly higher in the olanzapine group (70.0%) compared to the placebo group (56.1%), with a difference of 13.9% (one-sided P = 0.047). In the persistent phase, CR rates were again higher in the olanzapine group (63.9%) compared to the placebo group (44.4%). However, CR rates in the acute phase were similar between the two groups (92.5% vs. 92.7%). The no nausea rate was also higher in the olanzapine group in both the delayed and persistent phases. Continuous greater efficacy of olanzapine over placebo was observed throughout the 21-day observation period.

Somnolence occurred in 25.0% of patients in the olanzapine group compared to 10.8% in the placebo group, with no severe cases. Hyperglycemia was noted in 7.5% of the olanzapine group.

Overall, olanzapine demonstrated improved efficacy in reducing CR rates and nausea compared to placebo, with a favorable safety profile and positive patient-reported outcomes.

Nursing Considerations for Olanzapine Use

Oncology nurses play a crucial role in monitoring the severity and frequency of treatment-related symptoms, particularly nausea. Patients may sometimes be reluctant to take olanzapine due to its other indications, such as schizophrenia. Therefore, oncology nurses can provide essential education about the role of olanzapine, especially when combined with 5-HT3 receptor antagonists and dexamethasone, in effectively managing nausea. Additionally, it is important for nurses to monitor patients closely for potential side effects, such as somnolence.

In conclusion, effective management of nausea in patients receiving T-DXd is essential for improving treatment adherence and overall quality of life. The ERICA study highlights the efficacy of olanzapine in reducing delayed and persistent nausea when used in conjunction with standard antiemetic therapy, providing a valuable option for oncology nurses in their practice. By establishing clear protocols and offering thorough patient education, oncology nurses can enhance symptom management, mitigate treatment interruptions, and ensure a supportive environment for patients navigating breast cancer.

References

1. Sakai H, Tsurutani J, Ozaki Y, et al. 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). Ann Oncol. Published online September 14, 2024. doi:10.1016/j.annonc.2024.09.001

2. Notini G, Naldini MM, Sica L, et al. Management of Trastuzumab Deruxtecan-related nausea and vomiting in real-world practice. Front Oncol. 2024;14:1374547. Published 2024 Mar 11. doi:10.3389/fonc.2024.1374547