454P - A multicenter randomized open-label phase II study investigating optimal antiemetic therapy for patients with advanced/recurrent gastric cancer treated with trastuzumab deruxtecan (T-DXd): EN-hance study

Background

T-DXd is approved as 2L or later treatment for HER2-positive gastric cancer in several countries and is considered emetogenic. Nausea and vomiting affect significantly patient quality of life, leading to poor compliance with further treatment. Therefore, we sought to identify the optimal combination of antiemetic prophylaxis with T-DXd.

Methods

This study was a multicenter, randomized, open-label, non-comparative, Ph2 study to investigate optimal antiemetic prophylaxis for Japanese patients (pts) with gastric cancer treated with T-DXd. The pts were randomized to a doublet regimen (DxR, dexamethasone and palonosetron) or a triplet regimen (TxR, aprepitant in addition to doublet regimen) at a ratio of 1:1; stratified by gender, gastrectomy status, and study site. T-DXd admiration was started at 6.4 mg/kg and the antiemetic prophylaxis was administered from day 1 up to day 5. The primary endpoint was antiemetic complete response (CR, defined no emetic event and no rescue drug) rate to assess control emesis based on patient reported outcomes for 21 days. CR rate in acute phase (0-24hr) and delayed phase (2-21d) were evaluated as a secondary endpoint. With 29 pts per arm, the primary analysis considered a regimen promising if either arm had ≥18 CRs.

Results

A total of 58 pts were eligible for this analysis. Three pts were discontinued follow-up (2 pts in DxR, 1 pt in TxR). Both antiemetic CR rate for 21 days (overall) and CR rate in delayed phase were 41.4% (12/29) for DxR and 37.9% (11/29) for TxR. The antiemetic CR rate in acute phase was 86.2% (25/29) in both regimens. The median first emetic event occurred at 3 day in both regimens.

Conclusions

Both antiemetic prophylaxis regimens did not meet the prespecified antiemetic CR rate. This study, which used patient reported outcome to assess emetic events, has resulted in a higher rate of emetic events compare to monitoring by physicians reported in previous studies. Given the study design and small sample size, further research may help to fully characterize nausea and vomiting with T-DXd in gastric cancer pts.

Clinical trial identification

jRCTs031200336.

Editorial acknowledgement

Legal entity responsible for the study

Yokohama City University Hospital, Epidemiological and Clinical Research Information Network (ECRIN), and Daiichi Sankyo Co., Ltd.

Funding

Daiichi Sankyo Co., Ltd.

Disclosure

K. Oba: Financial Interests, Personal, Invited Speaker: Chugai, Daiichi Sankyo; Financial Interests, Personal, Other, IDMC member: Eisai, Ono pharmaceutical co, Janssen. K. Nishikawa: Financial Interests, Personal, Invited Speaker, Lecture fee: Bristol Myers Squibb, Daiichi Sankyo, EA Pharma, Eli Lilly, MSD, Ono, Taiho, Yakult. H. Maeda: Financial Interests, Personal, Invited Speaker: Tsumura Co; Financial Interests, Personal, Writing Engagement: Igaku-shoin; Non-Financial Interests, Personal, Other, journal editor: Annals of cancer research and therapy; Non-Financial Interests, Personal, Other, research advisory: Japanese foundation of multidisciplinary cancer treatment; Non-Financial Interests, Personal, Other, editorial board: Japanase society of human cells. A. Makiyama: Financial Interests, Personal, Invited Speaker: Eli Lilly, Taiho, Ono, Daiichi Sankyo, Bristol Myers Squibb. T. Oshima: Financial Interests, Personal, Invited Speaker: Taiho, Astellas; Financial Interests, Personal, Writing Engagement: Astellas; Financial Interests, Personal, Other, research grant: Taiho, Kyowa Kirin, Chugai, Nihon kayaku. A. Katayama: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo. K. Shiosakai: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo Co., Ltd. All other authors have declared no conflicts of interest.