| Study characteristics |
| Methods |
Randomised, parallel‐group, phase 3 trial with 2 arms
Recruitment period: n.r.
2322 patients enrolled, pre‐stratified by gender and randomised to treatment 2247 patients evaluated for efficacy
Masking: double‐blind
Baseline patient characteristics: reported
Follow‐up: n.r. |
| Participants |
Inclusion criteria
must have been scheduled to receive first course of cisplatin (≥ 70 mg/m²) for documented solid malignancy Karnofsky performance score ≥ 60 predicted life expectancy ≥ 3 months pre‐menopausal female patients of reproductive potential must have demonstrated a negative urine pregnancy test and agreed to use a double‐barrier form of contraception at least 14 days before and throughout the study, and for at least 1 month following the last dose of study medication must have been able to read, understand, and complete a study diary and questionnaire; understand study procedures; and give written informed consent
Exclusion criteria
symptomatic primary or metastatic central nervous system (CNS) malignancy radiation therapy to abdomen/pelvis in the week before treatment stem cell rescue therapy with cisplatin vomiting less than 25 h before treatment Day 1 treatment with multiple‐day chemotherapy with cisplatin in single cycle or moderately/highly emetogenic chemotherapy (< 6 days before and/or during the 6 days following cisplatin infusion) active infection or uncontrolled disease history of any illness that might confound results of the study or pose unwarranted risk in administering the study drug to the patient history of illicit drug use or alcohol abuse mental incapacitation or emotional or psychiatric disorder history of hypersensitivity to aprepitant, ondansetron, or dexamethasone breast‐feeding participated in an aprepitant/investigational drug study within 4 weeks of treatment Day 1 concurrent medication condition that would preclude administration of dexamethasone for 4 days had received systemic corticosteroid therapy had abnormal laboratory values
Median age (range), years: 56 (19 to 86) in i.v. fosaprepitant group, 57 (19 to 82) in oral aprepitant group
Gender: male + female
Tumour/cancer type: solid tumour (lung cancer, gastrointestinal cancer, reproductive or genitourinary cancer, miscellaneous or site unspecified, renal and urinary tract cancer, breast cancer, lymphoma, hepatic and biliary cancer, endocrine cancer)
Chemotherapy regimen: cisplatin at a dose ≥ 70 mg/m²
Country/continent: North America, South America, Europe, Asia‑Pacific, Africa |
| Interventions |
Experimental: arm A: i.v. fosaprepitant
Day 1: 150 mg fosaprepitant dimeglumine + 32 mg i.v. ondansetron + 12 mg p.o. dexamethasone
Day 2: 8 mg p.o. dexamethasone
Days 3 to 4: 8 mg p.o. dexamethasone twice a day
Experimental: arm B: p.o. aprepitant 125/80
Day 1: 125 mg p.o. aprepitant + 32 mg i.v. ondansetron + 12 mg p.o. dexamethasone
Days 2 to 3: 80 mg p.o. aprepitant + 8 mg p.o. dexamethasone
Day 4: 8 mg p.o. dexamethasone |
| Outcomes |
Primary endpoint
evaluating the non‐inferiority of fosaprepitant compared with aprepitant for complete response, defined as no vomiting and no use of rescue therapy, during the overall phase (120 h following initiation of cisplatin therapy)
Secondary endpoint(s)
assessment of the proportion of patients with complete response in the delayed phase (25 to 120 h following initiation of cisplatin therapy) assessment of the proportion of patients with no vomiting overall
|
| Notes |
study is registered with ClinicalTrials.gov, NCT00619359 "supported by Merck by provision of aprepitant and of financial support for the conduct of the study" conflicts of interest: "employment or leadership position: Suzanne DeVandry, Merck (C); Judith A. Boice, Merck (C); James S. Hardwick, Merck (C); Elizabeth Beckford, Merck (C); Arlene Taylor, Merck (C); Alexandra Carides, Merck (C); consultant or advisory role: Steven Grunberg, GlaxoSmithKline (C), Helsinn (C), Merck (C), Shin Nippon Biomedical Laboratories (C); Jose´ Dinis, Merck, Sharp, and Dohme (C); Fausto Roila, Merck (C), Helsinn (C); Jørn Herrstedt, GlaxoSmithKline (C); stock ownership: Steven Grunberg, Merck; Judith A. Boice, Merck; James S. Hardwick, Merck; Alexandra Carides, Merck Honoraria: Steven Grunberg, Merck; Fausto Roila, Merck, Helsinn, GlaxoSmithKline; Jørn Herrstedt, Merck; research funding: Fausto Roila, GlaxoSmithKline, Merck; Jørn Herrstedt, Merck, Helsinn; expert testimony: none; other remuneration: none |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Low risk |
Comment: patients were stratified by sex and were randomly assigned to treatment groups according to a computer‐generated, blinded allocation schedule |
| Allocation concealment (selection bias) |
Low risk |
Comment: to ensure in‐house blinding, treatment group assignments were made by personnel not otherwise involved with the study |
| Blinding of participants and personnel (performance bias)
Blinding of participants |
Low risk |
Quote: "... double‑blind ..." |
| Blinding of participants and personnel (performance bias)
Blinding of personnel |
Low risk |
Quote: "... double‑blind ..." |
| Blinding of outcome assessment (detection bias)
Subjective outcomes (Patient reported outcomes) |
Low risk |
Comment: both patients and personnel were blinded towards the intervention and thus had no influence on outcome assessment |
| Blinding of outcome assessment (detection bias)
Objective outcomes (including mortality and safety) |
Low risk |
Comment: both patients and personnel were blinded towards the intervention and thus had no influence on outcome assessment (e.g. infusion site reaction) |
| Incomplete outcome data (attrition bias)
Subjective outcomes (Patient reported outcomes) |
Low risk |
Comment: all patients were included from the efficacy analysis |
| Incomplete outcome data (attrition bias)
Objective outcomes (including mortality and safety data) |
Low risk |
Comment: all included patients were checked for adverse events |
| Selective reporting (reporting bias) |
Low risk |
Comment: all outcome measures were reported in the results section |
| Other bias |
Low risk |
Comment: no information to suggest other sources of bias |
