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Prophylactic Efficacy of Olanzapine-Based Therapy for Trastuzumab Deruxtecan–Associated Nausea and Vomiting in Patients With HER2-Positive or HER2-Low Breast Cancer
TAKE-HOME MESSAGE
- This randomized phase II trial evaluated data from 168 patients receiving trastuzumab deruxtecan (T-DXd) for HER2-positive or HER2-low metastatic breast cancer in Japan. Patients were randomized to receive olanzapine 5 mg or placebo daily from days 1 to 6 of the treatment cycle in addition to dexamethasone and a 5-hydroxytryptamine (5HT) type 3–receptor antagonist, such as ondansetron. Patients who received olanzapine were more likely to achieve a complete response, defined as no emetic events and no as-needed antiemetics used.
- We frequently use a triple antiemetic regimen for patients receiving T-DXd, which includes steroids, 5HT antagonists, and a neurokinin-1 receptor antagonist, such as aprepitant. These findings show that olanzapine also decreases the risk of nausea and emesis associated with T-DXd when used in combination with steroid and 5HT antagonist premedications.
abstract
This abstract is available on the publisher's site.
Access this abstract now Full Text Available for ClinicalKey SubscribersBACKGROUND
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 first cycle T-DXd.
PATIENTS AND METHODS
This multi-institutional, randomized, double-blind, placebo-controlled (ERICA) phase II study enrolled patients with HER2-positive/HER2-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 6, plus a 5-hydroxytryptamine type 3-receptor antagonist (5-HT3RA) and dexamethasone 6.6 mg intravenously or 8 mg orally on Day 1. The total observation period was 504 hours (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 hours post-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 hours), adverse event by CTCAE and PRO-CTCAE.
RESULTS
In total, 168 patients were enrolled at 43 sites in Japan (Nov 2021-Sep 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.
CONCLUSION
Olanzapine 5mg for 6 days with 5-HT3RA and dexamethasone appears effective for T-DXd-treated patients to prevent delayed and persistent nausea and vomiting.
Additional Info
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 2024 Sep 05;[EPub Ahead of Print], H Sakai, J Tsurutani, Y Ozaki, H Ishiguro, K Nozawa, T Yamanaka, K Aogi, K Matsumoto, T Iwasa, M Tokiwa, M Tsuneizumi, Y Miyoshi, C Kitazawa, M Yamamoto, Y Takano, CK Imamura, Y Chiba, D Takiguchi, T Ezumi, T TakanoFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.