1816O - A multicentre, randomized, double-blind, placebo-controlled study of olanzapine-based triplet antiemetic therapy for prevention of delayed and persistent nausea and vomiting induced by trastuzumab deruxtecan in patients with metastatic breast cancer: ERICA study (WJOG14320B)

Background

Nausea and vomiting (NV) are common side effects associated with trastuzumab deruxtecan (T-DXd) therapy. We evaluated the efficacy of olanzapine (OLZ) for the prevention of NV in patients (pts) receiving 1st cycle of T-DXd treatment.

Methods

ERICA was a randomized, double-blind, placebo (PBO)-controlled phase Ⅱ study. Pts with HER2-positive or HER2-low metastatic breast cancer (mBC) who were scheduled to receive T-DXd were enrolled. They were randomized to receive OLZ 5mg or PBO (once-daily) in a 1:1 ratio from day 1 to 6 in combination with 5-hydroxytryptamine type 3–receptor antagonist (5-HT₃RA) and dexamethasone (DEX: 6.6mg intravenously or 8mg orally on day 1). The observation period was 504 hours from the 1st T-DXd administration. The primary endpoint was complete response (CR; no emetic events and no rescue drugs) in the delayed phase (24-120 hours post-T-DXd), and the significance level for the comparison was set at 0.2 (one-sided). Endpoints included the no nausea rate in the delayed and persistent phases (120-504 hours), and patient-reported symptoms by PRO-CTCAE and adverse events.

Results

168 pts were enrolled at 43 sites in Japan between 11/2021 and 09/2023, and 162 pts (80 OLZ and 82 PBO) were included in the per protocol set. The study met its primary endpoint as the CR in the delayed phase was significantly greater with OLZ than PBO (70.0% vs 56.1%, p=0.047; difference (diff): 13.9%, 60%CI: 6.9 – 20.7). The no nausea rate was also significantly greater with OLZ than PBO (delayed phase: 57.5% vs 37.8%, p=0.009; diff: 19.7%, 95% CI: 3.1 – 34.6, persistent phase: 51.4% vs 31.9%, p=0.014; diff: 19.4%, 95% CI: 2.9 – 35.1). CR rates in the delayed phase favored OLZ over PBO across subgroups. Total days with nausea in 1st cycle were fewer for OLZ than PBO (4.0 vs 8.0 days, p=0.033). Appetite loss was less with OLZ than PBO (any grade: 60.0% vs 80.7%, p=0.006). Hyperglycemia and somnolence, mostly low-grade, were also observed with OLZ.

Conclusions

OLZ 5mg for 6 days with 5-HT₃ RA and DEX could be an effective option for pts treated with T-DXd to reduce delayed and persistent NV.

Clinical trial identification

jRCTs031210410.

Editorial acknowledgement

Under the guidance of authors, editorial assistance was provided by Steve Clissold PhD and was funded by Daiichi Sankyo Co, Ltd.

Legal entity responsible for the study

West Japan Oncology Group, Daiichi Sankyo.

Funding

Daiichi Sankyo Co., Ltd.

Disclosure

H. Sakai: Financial Interests, Personal, Invited Speaker, speaker honorarium: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Eli Lilly, Chugai Pharmaceutical Co., Ltd, Gilead Sciences; Non-Financial Interests, Personal, Other, medical writing support: Daiichi Sankyo. J. Tsurutani: Financial Interests, Personal, Advisory Board: Daiichi Sankyo, AstraZeneca, Eisai Inc., Daiichi Sankyo, Taiho Inc.; Financial Interests, Personal, Member of Board of Directors: West Japan Oncology Group; Financial Interests, Institutional, Research Grant: Eisai, Eli Lilly, Ono; Financial Interests, Institutional, Funding: Daiichi Sankyo, West Japan Oncology Group; Financial Interests, Institutional, Coordinating PI: FSJD. Y. Ozaki: Financial Interests, Personal, Invited Speaker, Honoraria: Daiichi Sankyo, Pfizer, Eli Lilly, Kyowa Kirin. H. Ishiguro: Financial Interests, Personal, Invited Speaker: MSD K.K, AstraZeneca, Kyowa Kirin Co., Ltd., Taiho Pharmaceutical Co., Ltd, Daiichi Sankyo, Chugai Pharmaceutical Co, Eisai Co, Ltd.; Financial Interests, Personal, Other, Consultation: Mitsubishi Tanabe Pharma Corporation; Financial Interests, Institutional, Local PI: NIPRO CORPORATION, Chugai Pharmaceutical Co., Ltd, Takeda Pharmaceutical Company Limited, Daiichi Sankyo, MSD K.K., Eisai Co., Ltd. T. Yamanaka: Financial Interests, Personal, Invited Speaker, Honoraria for lecture: Daiichi Sankyo, Eli Lilly Japan, Chugai, Pfizer, Kyowa-Kirin, AstraZeneca, Taiho. H. Kameoka: Financial Interests, Personal, Invited Speaker: MSD, Nippon Kayaku. K. Matsumoto: Financial Interests, Personal, Other, Honoraria: MSD, Kyowa Kirin, Daiichi Sankyo, Eli Lilly, Chugai; Financial Interests, Institutional, Local PI: Daiichi Sankyo, MSD, Eli Lilly, Gilead Sciences, Eisai. Y. Miyoshi: Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, Chugai, ISAO, Eli Lilly, AstraZeneca, Pfizer, Taiho, Kyowa-Kirin; Financial Interests, Institutional, Local PI: Daiichi Sankyo, Eisai, MSD, Eli Lilly; Financial Interests, Institutional, Research Grant: Chugai, Kyowa-Kirin, Taiho. C. Kitagawa: Financial Interests, Personal, Invited Speaker: Ono Yakuhin, Chugai Pharma, Daiichi Sankyo; Financial Interests, Institutional, Local PI: Daiichi Sankyo/AstraZeneca, Sanofi, MSD, AbbVie, ALX oncology, Ono Takuhin. Y. Takano: Financial Interests, Personal, Invited Speaker: Chugai Pharma Co, Ltd., Eli Lilly and Company, MSD, Daiichi Sankyo Co, Ltd. C.K. Imamura: Financial Interests, Personal, Funding: Eli Lilly Japan K.K. D. Takiguchi: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. T. Ezumi: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. T. Takano: Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, Chugai, Eli Lilly. All other authors have declared no conflicts of interest.