Kusagaya 2015.

Study characteristics
Methods	Randomised, controlled, prospective, parallel‐group trial with 2 arms comparison of aprepitant + palonosetron + dexamethasone vs palonosetron + dexamethasone Enrolment period: April 2013 to February 2015 81 patients enrolled and randomised Masking: open‐label Baseline patient characteristics: reported Follow‐up: n.r.
Participants	Inclusion criteria aged ≥ 20 years chemotherapy‐naïve with pathologically confirmed inoperable stage IIIB or IV NSCLC ECOG performance status 0 or 1 receiving carboplatin‐based chemotherapy adequate hematopoietic, renal, and hepatic function Exclusion criteria nausea and vomiting within 24 h use of antiemetic agents and corticosteroids within 24 h before administration of chemotherapy use of pimozide uncontrolled diabetes mellitus conditions likely to induce emesis regardless of chemotherapy, including symptomatic brain metastasis, gastrointestinal obstruction, and active gastrointestinal ulcer pregnant female, nursing mom Median age, years: 70 (57 to 90) in aprepitant group, 73 (43 to 84) in control group Gender: male (57) + female (23) Tumour/cancer type: non‐small cell lung cancer Chemotherapy regimen: carboplatin + paclitaxel, carboplatin + paclitaxel + bevacizumab, carboplatin + pemetrexed, carboplatin + pemetrexed + bevacizumab, carboplatin + S‐1 Country: Japan (multi‐centre)
Interventions	Experimental: arm A: aprepitant Day 1: aprepitant 125 mg + palonosetron 0.75 mg + dexamethasone 8 mg Days 2 to 3: aprepitant 80 mg + dexamethasone 8 mg Control: arm B Day 1: palonosetron 0.75 mg + dexamethasone 8 mg Days 2 to 3: dexamethasone 8 mg
Outcomes	Primary endpoint complete response rate in the overall phase (during 120 h after chemotherapy administration) Secondary endpoint(s) complete response rate in acute (first 24 h after chemotherapy administration) and delayed phases (24 to 120 h after chemotherapy) nausea in overall, acute, and delayed phases safety
Notes	trial was registered with University Hospital Medical Information Network (UMIN) Clinical Trial Registry: UMIN000010056 funding source: Hamamatsu University School of Medicine conflicts of interest: "all authors declare no actual or potential conflicts of interest"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "randomization was performed centrally by computer software and stratified by sex, age, and non‐platinum chemotherapy agent"
Allocation concealment (selection bias)	Unclear risk	Comment: allocation concealment was not reported
Blinding of participants and personnel (performance bias) Blinding of participants	High risk	Quote: "... open‐label ..."
Blinding of participants and personnel (performance bias) Blinding of personnel	High risk	Quote: "... open‐label ..."
Blinding of outcome assessment (detection bias) Subjective outcomes (Patient reported outcomes)	High risk	Comment: patients and personnel were not blinded towards the intervention and therefore might influence subjective outcomes analysis
Blinding of outcome assessment (detection bias) Objective outcomes (including mortality and safety)	Low risk	Comment: although this was an open‐label study, both patients and personnel had no influence on objective outcomes (e.g. neutropenia, hiccups)
Incomplete outcome data (attrition bias) Subjective outcomes (Patient reported outcomes)	Low risk	Quote: "one patient withdrew consent before chemotherapy, and 80 patients (41 in the aprepitant group and 39 in the control group) were assessed for efficacy and safety"
Incomplete outcome data (attrition bias) Objective outcomes (including mortality and safety data)	Low risk	Quote: "one patient withdrew consent before chemotherapy, and 80 patients (41 in the aprepitant group and 39 in the control group) were assessed for efficacy and safety"
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