Vansteenkiste 2016

Methods	International multicenter RCT (590 centres in 34 countries), Phase III
Participants	Number of participants: 2312 (Oct 18, 2007, and July 17, 2012) Number randomised: Experimental group (recMAGE‐A3 with AS15 immunostimulant): 1541 Control group (placebo): 771 Number evaluated: Experimental group: 1515, age (median and range): 63 (57 to 70) years Control group: 757, age (median and range): 63 (57 to 70) years Diagnosis: patients with completely resected stage IB, II, and IIIA MAGE‐A3‐positive NSCLC who did or did not receive adjuvant chemotherapy. Inclusion: eligible patients should be: > 18 years; Male or female patient with completely resected, pathologically proven stage IB, II or IIIA NSCLC; tumour shows expression of MAGE‐A3 gene; the surgical technique for resection of the patient's tumour is anatomical, involving at least a lobectomy or a sleeve lobectomy; ECOG performance status of 0, 1 or 2 at the time of randomisation; adequate bone‐marrow reserve, adequate renal function, and adequate hepatic function as assessed by standard laboratory criteria, and defined as: absolute neutrophil count ≥ 1.0 x 10E9/L Platelet count ≥ 75 x 10E9/L, serum creatinine ≤ 1.5 times, the Upper Limit of Normal (ULN) ≤ 3.0 times, the ULN if due to platinum adjuvant chemotherapy, total bilirubin ≤ 1.5 times the ULN Alanine transaminase (ALAT) ≤ 2.5 times the ULN.
Interventions	Experimental group : participants received GSK1572932A Antigen‐Specific up to 13 intramuscular injections during 27 months. Five doses were given every 3 weeks, followed by eight doses every 12 weeks. Control group : participants received placebo up to 13 intramuscular injections during 27 months. Five doses were given every 3 weeks, followed by eight doses every 12 weeks. Treatment started at the time of randomisation.
Outcomes	Duration of follow‐up (median): Experimental group: 38.1 months (IQR 27.9 to 48.4), control group：39.5 months (IQR 27.9 to 50·4) disease‐free survival, overall survival, quality of life, adverse event.
Notes	This study was designed, funded, and interpreted by GlaxoSmithKline in cooperation with an international steering committee.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Randomisation at the investigator site was done centrally via Internet with stratification for chemotherapy versus no chemotherapy. Within each chemotherapy stratum, a minimisation algorithm was used to allocate study group, accounting for the number of chemotherapy cycles received (1 to 2 or 3 to 4), disease stage (IB, II, or IIIA), lymph node sampling procedure (mediastinal lymph node dissection or sampling), PS score (0 to 1 or 2), and lifetime smoking status (never, past, or current)"
Allocation concealment (selection bias)	Low risk	The randomisation was done centrally, so that the researchers would have no way of knowing in advance the allocation of the next participant.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Individual treatment assignment was masked at all levels, masking was managed by the central randomisation system with access limited to a single sponsor database administrator who was independent from the trail
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Individual treatment assignment was masked at all levels, masking was managed by the central randomisation system with access limited to a single sponsor database administrator who was independent from the trail
Incomplete outcome data (attrition bias) All outcomes	Low risk	All randomised participants were included in analysis (100%)
Selective reporting (reporting bias)	Low risk	Prior protocol was available
Other bias	Low risk	No obvious potential source of bias