A multicenter randomized open-label phase 2 study investigating optimal antiemetic therapy for patients with advanced/recurrent gastric cancer treated with trastuzumab deruxtecan: the EN-hance study.

[BACKGROUND] Trastuzumab deruxtecan (T-DXd) has been approved for the treatment of human epidermal growth factor receptor-2 (HER2)-positive gastric cancer and other indications in several countries and is considered moderately or highly emetogenic. The management of nausea and vomiting associated with T-DXd treatment has not been fully evaluated and the effectiveness of conventional prophylaxis remains unknown.

[METHODS] This open-label, randomized, multicenter, phase 2 study aimed to investigate the optimal antiemetic therapy for Japanese patients with gastric cancer undergoing T-DXd treatment. Patients were randomized to a doublet regimen group (dexamethasone and palonosetron) or triplet regimen group (aprepitant, dexamethasone, and palonosetron) at a ratio of one to one, stratified by sex, gastrectomy status, and study institution. Both antiemetic treatments were administered from day 1 before T-DXd administration, and emetic events and nausea were observed for 21 days. The primary endpoint was the antiemetic complete response (CR) rate to assess control for emetic events based on voluntary patient-reported outcomes (PROs) during cycle 1 (1-21 days).

[RESULTS] Of the 60 enrolled patients, 58 were eligible for inclusion in this analysis (29 patients in each regimen group). The overall CR rates for the doublet and triplet regimens were 41.4% (12/29 patients) and 37.9% (11/29 patients), respectively, and neither regimen met the pre-specified threshold (> 18/29 patients). The CR rate in the acute phase (0-24 h) was 86.2% (25/29 patients) for both regimens, and the CR rates in the delayed phase (2-21 days) were 41.4% (12/29 patients) and 37.9% (11/29 patients) for the doublet and triplet regimens, respectively.

[CONCLUSIONS] Given that the primary endpoint was not met, further research is needed to better characterize nausea and vomiting with T-DXd to tailor an anti-emetic regimen that suits the needs of the patients.