Incidence and severity of nausea and vomiting with trastuzumab deruxtecan: a systematic review and meta-analysis

INTRODUCTION: Trastuzumab deruxtecan (T-DXd) is associated with chemotherapy-induced nausea and vomiting (CINV), yet the incidence, severity, and optimal antiemetic prophylaxis remain uncertain. We conducted a systematic review and meta-analysis to quantify T-DXd-related nausea and vomiting and evaluate the effectiveness of triplet vs doublet prophylaxis. METHODS: Following PRISMA guidelines, we searched Ovid MEDLINE® ALL, Embase, and the Cochrane Library (1946 to June 2025) for studies reporting nausea and vomiting outcomes with T-DXd. The primary endpoint was pooled incidence of nausea and vomiting. Secondary endpoints included relative risk compared with standard therapies and comparative effectiveness of triplet vs doublet antiemetic prophylaxis. FINDINGS: Thirty-two studies including 5365 patients (4224 T-DXd recipients) met inclusion. At the 5.4 mg/kg dose, pooled incidence was 65% for any-grade nausea and 31% for any-grade vomiting, with ≥ grade 3 events ≤4%. Incidence rates were similar at 6.4 mg/kg, with no significant dose-dependent increase in gastrointestinal toxicity (RR 0.96; 95% CI 0.83-1.11). Across five randomized trials, T-DXd significantly increased the risk of any-grade nausea 70.8% vs 28.4% (RR 2.29; 95% CI 1.74-3.02) and vomiting (RR 3.49; 95% CI 2.78-4.38) compared with standard therapies, while high-grade events remained uncommon (≤4%). Triplet antiemetic prophylaxis significantly improved delayed-phase nausea control (RR 1.27; 95% CI 1.03-1.58). INTERPRETATION: Nausea and vomiting, particularly delayed nausea, are common with T-DXd, representing a major unmet supportive-care need. Triplet antiemetic prophylaxis improves delayed nausea control and should be considered. Future prospective studies incorporating patient-reported outcomes are needed to optimize prophylactic strategies. FUNDING: None.