Rapoport 2015 (c).

Study characteristics
Methods	Randomised, parallel‐group, active‐controlled, phase 3 trial with 2 arms comparison of rolapitant + granisetron + dexamethasone vs placebo + granisetron + dexamethasone Study period: February 2012 to March 2014 555 patients randomised Masking: double‐blind Baseline patient characteristics: reported Follow‐up: yes
Participants	Inclusion criteria 18 years of age or older, of either gender, of any race never treated with cisplatin and is to receive first course of cisplatin‐based chemotherapy (≥ 60 mg/m²) Karnofsky performance score ≥ 60 predicted life expectancy ≥ 4 months adequate bone marrow, kidney, and liver function Exclusion criteria contraindication to cisplatin, granisetron, or dexamethasone pregnant or breast‐feeding has previously received cisplatin or is planning to receive multiple days of cisplatin in a single cycle has taken the following agents within the last 48 h: 5‐HT₃ antagonists, phenothiazines, benzamides, domperidone, cannabinoids, NK₁ antagonists, benzodiazepines scheduled to receive any other chemotherapeutic agent with emetogenicity level ≥ 4 (Hesketh Scale) from Day 2 through Day 6, except on Day 1 scheduled to receive any radiation therapy to abdomen or pelvis from Day ‐5 through Day 6 has received systemic corticosteroids or sedative antihistamines within 72 h of Day 1 of the study except as pre‐medication for chemotherapy (e.g. taxanes, pemetrexed) symptomatic primary or metastatic CNS disease ongoing vomiting, retching, clinically significant nausea caused by any aetiology, or history of anticipatory nausea and vomiting has vomited and/or has had dry heaves/retching within 24 h before the start of cisplatin‐based chemotherapy on Day 1 in Cycle 1 Mean age ± SD, years: 58.5 ± 10.05 in rolapitant group, 58.5 ± 9.25 in placebo group Gender: male (369) + female (175) Tumour/cancer type: solid tumour (breast, colon or rectum, head and neck, lung, ovary, stomach, and other tumours) Chemotherapy regimen: cisplatin‐based chemotherapy (≥ 60 mg/m²) Country: United States (multi‐centre)
Interventions	Experimental: arm A: rolapitant Day 1: oral dose of rolapitant 180 mg (equivalent to 200 mg rolapitant hydrochloride monohydrate) 1 to 2 h before administration of chemotherapy + granisetron (10 µg/kg i.v.) + dexamethasone (20 mg p.o.) Days 2 to 4: dexamethasone (8 mg p.o.) to be administered orally b.i.d. Control: arm B Day 1: placebo + granisetron (10 µg/kg i.v.) + dexamethasone (20 mg p.o.) Days 2 to 4: dexamethasone (8 mg p.o.) to be administered orally b.i.d.
Outcomes	Primary endpoints no emetic episodes and no rescue medication [Time frame: > 24 to 120 h post chemotherapy] Secondary endpoints acute phase response [Time frame: 0 to 24 h] overall response rate [Time frame: 0 to 120 h]
Notes	clinicalTrials.gov Identifier: NCT01500213 sponsors and collaborators: Tesaro, Inc. "the study sponsor was also unaware of treatment allocation" conflicts of interest: "BLR and IDS are advisory board consultants for the sponsor TESARO, outside the submitted work. AP and VK are employees of the sponsor TESARO. SA has received contracting fees from TESARO during this study and outside the submitted work. LSS is a consultant for TESARO, Helsinn, and Eisai, outside the submitted work. All other authors declare no competing interests"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "for randomisation of patients, we used an interactive web‐based randomisation system (IWRS) at cycle 1"
Allocation concealment (selection bias)	Low risk	Quote: "an independent group not involved with study implementation created a randomisation schedule for study drug labelling"
Blinding of participants and personnel (performance bias) Blinding of participants	Low risk	Quote: "double‐blind (participant, investigator)"
Blinding of participants and personnel (performance bias) Blinding of personnel	Low risk	Quote: "double‐blind (participant, investigator)"
Blinding of outcome assessment (detection bias) Subjective outcomes (Patient reported outcomes)	Low risk	Comment: both patients and personnel were blinded towards the intervention; therefore they probably 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. febrile neutropenia, neutropenia)
Incomplete outcome data (attrition bias) Subjective outcomes (Patient reported outcomes)	Low risk	Comment: analysis included modified ITT population
Incomplete outcome data (attrition bias) Objective outcomes (including mortality and safety data)	Low risk	Quote: "the safety population included all patients who were randomly allocated to a treatment group and who received at least one dose of study drug"
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