Background: Advances in antiemetic supportive care have led to remarkable improvements in the prevention of CINV, with evidence-based antiemetic guidelines, such as NCCN, recommending multi-agent prophylactic combinations that target different receptors. Clinical trials have confirmed the superiority of triple combination regimens (an NK 1 receptor antagonist [NK 1 RA], a 5-HT 3 RA, and dexamethasone [DEX]) over a 5-HT 3 RA + DEX. Thus, a triple combination is indicated for patients receiving HEC. In the clinical development program of NEPA, 3 HEC (cisplatin-based) registration studies included an NK 1 RA (aprepitant; APR) + 5-HT 3 RA + DEX arm. This post-hoc analysis evaluated the efficacy of NEPA versus APR across the cisplatin trials. Methods: Chemotherapy-naïve patients in 3 randomized, double-blind, multinational trials received a single oral dose of NEPA + DEX prior to cisplatin on Day 1 or a 3-day APR comparator/control regimen. All patients in both groups also received DEX on Days 2-4. Inclusion/exclusion criteria were similar across studies. Data from the 3 studies were pooled for efficacy endpoints of: 1) complete response (CR: no emesis, no rescue medication); 2) no significant nausea (NSN: max <25 mm on 100 mm VAS); and 3) complete protection (CP: no emesis, no rescue and NSN) for the post-chemotherapy acute (0-24 h), delayed (25-120 h) and overall (0-120 h) phases. Treatments and associated risks were compared using generalized linear models with log-link function and binomial distribution (log-binomial model). Results: In this pooled analysis, 621 patients received NEPA and 576 received APR. Although response rates were similar for the acute phase, delayed and overall phase responses favored NEPA (Table). Conclusions: Based on the current pooled analysis of Phase 3, cisplatin-based studies, oral NEPA administered on Day 1 only was more effective than a 3-day APR regimen in preventing delayed and overall CINV from HEC. NEPA, a fixed oral combination of an NK 1 RA/5HT 3 RA in a single capsule administered only once per cycle, offers clinicians a simple, convenient, and highly effective prophylactic combination antiemetic concordant with guidelines. Other potential benefits include reducing healthcare costs associated with decreased acute-care use related to delayed CINV, and minimizing the risk for suboptimal patient adherence to antiemetics.