Phase III results for the novel neurokinin-1 (NK-1) receptor antagonist, casopitant: 3-day IV/oral dosing regimen for chemotherapy-induced nausea and vomiting (CINV) in patients (Pts) receiving moderately emetogenic chemotherapy (MEC)

Abstract

20512 Background: In a phase III trial, 3 dosing regimens of casopitant, a novel NK-1 receptor antagonist, were evaluated for efficacy in reducing the number of pts experiencing emesis from initial and subsequent cycles of MEC: single oral, 3-day oral, and 3-day IV/oral dosing. Reported here are the results for the 3-day IV/oral regimen of casopitant combined with ondansetron/dexamethasone (OND/DEX) for pts receiving anthracycline and cyclophosphamide (AC)-based MEC. Methods: This multinational, double-blind, active-controlled trial included 1933 pts with breast cancer (96%). All pts received DEX 8 mg IV D1 + OND 8 mg BID PO D1–3. Pts were randomized to receive no additional therapy (CTRL), a 3-day IV/oral regimen (90 mg IV D1 + 50 mg PO D2–3), a single oral dose (150 mg PO D1), or a 3-day oral dose (150 mg PO D1 + 50 mg PO D2–3) of casopitant. Pts continued on therapy up to 4 cycles. Complete Response (CR; no vomiting/retching, rescue medications) in the first 120 hrs after each cycle of an AC-based MEC regimen was the primary endpoint. Results: Addition of a 3-day IV/oral regimen of casopitant to OND/DEX produced a statistically significant improvement (at a 1.67% level of significance adjusted for three primary comparisons) in overall CR rates compared with CTRL, which appeared to be maintained through 4 cycles of MEC. Casopitant was generally well tolerated with AE frequency similar across the arms. Common AEs were neutropenia, alopecia, fatigue, leukopenia, and constipation. Conclusions: A 3-day IV/oral dosing regimen of casopitant added to OND/DEX provided a clinically meaningful improvement in the reduction of emetic events in pts receiving initial and repeat cycles of MEC. Over all cycles, casopitant was generally well tolerated. Cycle of MEC Endpoints (0–120 hrs) CTRL n=479 (%) Casopitant 90 mg IV D1 + 50 mg PO D2–3 n=479 (%) P- value 1 Complete Response 284/479 (59) 353/479 (74) <0.0001 Acute (0–24 hrs) 406 (85) 412 (86) 0.5835 Delayed (24–120 hrs) 284 (59) 353 (74) <0.0001 No vomiting 304 (63) 373 (78) <0.0001 2 Complete Response 236/377 (63) 308/378 (81) NA 3 Complete Response 222/333 (67) 276/343 (80) NA 4 Complete Response 200/289 (69) 254/304 (84) NA Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline