Granisetron transdermal delivery system versus palonosetron in the prevention of long-delayed nausea and vomiting: a phase III randomized trial

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) significantly impact the patients' quality of life. Whether the granisetron transdermal delivery system (GTDS) offers better protection than palonosetron against long-delayed (120-168 hours) CINV after highly or moderately emetogenic chemotherapy (HEC/MEC) had not been prospectively tested. METHODS: A multicenter, randomized clinical study was conducted in China. Patients scheduled to receive either HEC or MEC were randomly assigned (1:1) to GTDS or palonosetron, each in combination with a neurokinin-1 receptor antagonist (NK1-RA) and dexamethasone. The primary endpoint was the complete response (CR; no vomiting and no rescue medication) rate during the long-delayed phase (120-168 hours), stratified by HEC and MEC categories, to demonstrate the superiority of GTDS over palonosetron. RESULTS: Overall, 150 patients received either GTDS or palonosetron respectively. We found that the GTDS group demonstrated a significantly higher long-delayed CR rate (97.3%) than the palonosetron group (92%) (P = .04). This advantage was driven predominantly by the HEC subgroup (GTDS 97.5% vs palonosetron 90.8%, P = .028). No significant differences were observed between the groups for the acute (0-24 hours, 92.7% vs 90.0%; P = .412), delayed (24-120 hours, 80.0% vs 76.0%; P = .403), extended-delayed (24-168 hours, 80.7% vs 75.3%; P = .265), or overall (0-168 hours, 78.0% vs 74.0%; P = .417) phases. CONCLUSION: A GTDS-based triple antiemetic regimen can effectively control CINV associated with HEC or MEC. It provides a convenient alternative route for delivering granisetron for up to 7 days, with superior efficacy in controlling long-delayed CINV. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT04912271 (in-house ethic number: YBCSG-21-04).