Phase III results of a novel oral neurokinin-1 (NK-1) receptor antagonist, casopitant: Single oral and 3-day oral dosing regimens for chemotherapy-induced nausea and vomiting (CINV) in patients (pts) receiving moderately emetogenic chemotherapy (MEC)

Abstract

9540 Background: In a phase II dose-ranging trial, casopitant, a novel NK-1 antagonist, plus ondansetron/dexamethasone (OND/DEX) demonstrated efficacy in reducing CINV in pts receiving MEC. This phase III trial evaluated three dosing regimens in pts receiving anthracycline and cyclophosphamide (AC)-based MEC. Methods: 1,933 pts with breast cancer (96%) were enrolled in a multinational, double-blind, active-controlled trial. 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 single oral dose (150 mg PO D1), or a 3-day oral or 3-day IV/oral dose (150 mg PO D1 or 90 mg IV D1 + 50 mg PO D2–3) of casopitant. Pts continued on therapy up to 4 cycles. Complete response (CR; no vomiting, retching, or rescue medications) in the first 120 hrs after each cycle of an AC-based MEC regimen was the primary endpoint. Here we report on pts receiving the oral dosing regimens of casopitant in addition to CTRL. Results: Both single oral dose and 3-day oral regimens of casopitant plus OND/DEX produced statistically significant improvement (at a 1.67% level of significance adjusted for 3 primary comparisons) in overall CR rates over 5 days. This clinical benefit appeared to be maintained through repeat cycles of MEC. Significant reductions in the number of pts experiencing emetic events in the overall and delayed phases were observed. Casopitant was generally well tolerated. AE frequency was similar across study arms. Common Aes were neutropenia, alopecia, fatigue, leukopenia, and constipation. Conclusions: Addition of a single oral dose or a 3-day oral regimen of casopitant to OND/DEX provided a clinically meaningful improvement in the proportion of patients achieving CR over 5 days. This benefit appeared to be maintained in initial and repeat cycles of MEC. The casopitant regimens were generally well tolerated over all cycles. Cycle of MEC Endpoints (0–120 hrs) CTRL n=479 (%) Casopitant 150 mg PO D1 n=479 (%) P-value 150 mg PO D1+50 mg PO D2–3 nCTRL n=479 (%)480 (%) P- value 1 Complete Response 284 (59) 351 (73) <0.0001 350 (73) <0.0001 Acute (0–24 hrs) 406 (85) 421 (88) 0.1586 427 (89) 0.0545 Delayed (24–120 hrs) 284 (59) 351 (73) <0.0001 350 (73) <0.0001 No vomiting 304 (63) 381 (80) <0.0001 387 (81) <0.0001 2 Complete Response 236/377 (63) 307/383 (80) NA 308/378 (81) NA 3 Complete Response 222/333 (67) 274/345 (79) NA 276/343 (80) NA 4 Complete Response 200/289 (69) 250/306 (82) NA 254/304 (84) NA Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline, Helsinn, Merck, Schering-Plough GlaxoSmithKline Helsinn, Merck GlaxoSmithKline