Phase III randomized double-blind study of single-dose fosaprepitant for prevention of cisplatin-induced nausea and vomiting.

Abstract

9021^ Background: Addition of a neurokinin-1 antagonist (NK1A) to a standard ondansetron (O) and dexamethasone (D) antiemetic regimen improves prevention of cisplatin-induced nausea/vomiting (CINV), particularly during the delayed period (25-120 hours) (DP). Therefore approved regimens include multiple day NK1A administration extending into the DP. Preliminary data (Grunberg, Supp Care Cancer 17:589, 2009) suggested that a single NK1A dose prior to chemotherapy could give excellent CINV protection throughout the overall period of risk (0-120 hours) (OP). The present study compared the approved schedule of oral NK1A aprepitant (Emend) (A) to single-dose intravenous NK1A fosaprepitant (Emend for Injection) (F). Methods: A randomized double-blind active-control design was used to test whether F is non-inferior to A. Patients (pts) receiving cisplatin ≥70 mg/m2 for the first time received O and D with a standard A regimen (125 mg day 1, 80 mg day 2, 80 mg day 3) or an abbreviated F regimen (150 mg day 1). Primary endpoint was Complete Response (no vomiting, no rescue medication) (CR) during OP. Secondary endpoints were CR during DP and no vomiting (NV) during OP. Accrual of 1,113 evaluable pts per arm was required to confirm non-inferiority with expected CR of 67.7% and non-inferiority margin of 7 percentage points. Adverse events were observed and recorded. Results: 2,322 pts were entered, with 2,247 considered evaluable for efficacy (1,138 receiving A and 1,109 receiving F). Antiemetic protection was similar between A and F within predefined bounds in terms of CR OP (72.3% vs. 71.9%), CR DP (74.2% vs. 74.3%) and NV OP (74.6% vs. 72.9%). Both regimens were well tolerated, although more frequent infusion site pain/erythema/phlebitis was seen with F (0.6% vs. 2.4%). Conclusions: Given with O and D, a single-day regimen of F was non-inferior to a standard 3-day regimen of A in preventing CINV during OP and DP. Equivalence of these regimens allows more convenient administration of an NK1A but also raises question as to whether the key variable in NK1A antiemetic protection during DP is serum drug exposure, duration of receptor occupancy, or timing of antiemetic administration (prior to the emetogenic challenge). Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck Merck Merck Merck Merck In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519-521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2010 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest.