Phase III results for the novel neurokinin-1 (NK-1) receptor antagonist, casopitant: Single oral dosing regimen for chemotherapy-induced nausea and vomiting (CINV) in patients (Pts) receiving highly emetogenic chemotherapy (HEC)

Abstract

9549 Background: In a phase II dose-ranging trial, casopitant, a novel NK-1 receptor antagonist, demonstrated efficacy in preventing CINV in pts receiving HEC. This Phase III trial evaluated 2 casopitant dosing regimens, here we present results of a single oral dose of casopitant (150 mg) added to ondansetron/dexamethasone (OND/DEX) for the prevention CINV events in pts receiving HEC. Methods: This multinational, double-blind, active-controlled trial included 810 pts, with 99% receiving cisplatin-based HEC regimens for up to 6 cycles. Pts were randomized to receive no additional therapy (CTRL; OND 32 mg IV + DEX 20 mg PO), or a single dose casopitant arm (150 mg PO + OND 32 mg IV + DEX 12 mg PO) D1, plus DEX 8 mg PO BID D2–4 for all pts. An additional arm evaluated a 3-day IV/oral dose (casopitant 90 mg IV + OND 32 mg IV + DEX 12 mg PO) on D1 plus casopitant 50 mg PO D2–3 + DEX 8 mg PO QD D2–4. Complete Response (CR; no vomiting/retching, rescue medications) in the first 120 hours of HEC was the primary endpoint. Results: In the first 5 days of cycle 1, pts receiving a single oral dose of casopitant achieved a statistically significant improvement (2.5% level of significance adjusted for 2 primary comparisons) in CR rates compared with CTRL. This clinical benefit appeared to be maintained in cycles 2–6 of HEC. Significant improvements were observed in CR in the acute and delayed phases. Clinically meaningful improvements in the secondary endpoints of no significant nausea (SN), and no nausea were also observed. AEs occurred with similar frequency in all arms. Common AEs were neutropenia, leukopenia and anemia. Conclusions: A single oral dose of casopitant added to a regimen of OND/DEX provided a clinically significant reduction in the number of pts experiencing CINV events over the first 5 days after HEC. This benefit appeared to be maintained through repeat cycles. This regimen was generally well tolerated over all cycles. Cycle of HEC Endpoints (0–120 hrs) CTRL n=265 (%) 150 mg PO D1 n=266 (%) P-value 1 Complete Response 175 (66) 228 (86) <0.0001 Acute (0–24 hrs) 234 (88) 253 (95) 0.0044 Delayed (24–120 hrs) 175 (66) 228 (86) <0.0001 No vomiting 179 (68) 236 (89) <0.0001 No SN (VAS < 25 mm) 184 (69) 207 (78) 0.0272 No nausea (VAS <5 mm) 121 (46) 151 (57) 0.0105 2 Complete Response 113/146 (77) 123/131 (94) NA 3 Complete Response 92/118 (78) 89/97 (92) NA 4 Complete Response 66/89 (74) 70/75 (93) NA 5 Complete Response 13/15 (97) 10/11 (91) NA 6 Complete Response 5/9 (56) 9/9 (100) NA Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline