BACKGROUND: Fewer than half of the patients with completely resected 
non-small-cell lung cancer (NSCLC) are cured. Since the introduction of adjuvant 
chemotherapy in 2004, no substantial progress has been made in adjuvant 
treatment. We aimed to assess the efficacy of the MAGE-A3 cancer 
immunotherapeutic in surgically resected NSCLC.
METHODS: In this randomised, double-blind, placebo-controlled trial, we 
recruited patients aged at least 18 years with completely resected stage IB, II, 
and IIIA MAGE-A3-positive NSCLC who did or did not receive adjuvant chemotherapy 
from 443 centres in 34 countries (Europe, the Americas, and Asia Pacific). 
Patients were randomly assigned (2:1) to receive 13 intramuscular injections of 
recMAGE-A3 with AS15 immunostimulant (MAGE-A3 immunotherapeutic) or placebo 
during 27 months. Randomisation and treatment allocation at the investigator 
site was done centrally via internet with stratification for chemotherapy versus 
no chemotherapy. Participants, investigators, and those assessing outcomes were 
masked to group assignment. A minimisation algorithm accounted for the number of 
chemotherapy cycles received, disease stage, lymph node sampling procedure, 
performance status score, and lifetime smoking status. The primary endpoint was 
broken up into three co-primary objectives: disease-free survival in the overall 
population, the no-chemotherapy population, and patients with a potentially 
predictive gene signature. The final analyses included the total treated 
population (all patients who had received at least one treatment dose). This 
trial is registered with ClinicalTrials.gov, number NCT00480025.
FINDINGS: Between Oct 18, 2007, and July 17, 2012, we screened 13 849 patients 
for MAGE-A3 expression; 12 820 had a valid sample and of these, 4210 (33%) had a 
MAGE-A3-positive tumour. 2312 of these patients met all eligibility criteria and 
were randomly assigned to treatment: 1515 received MAGE-A3 and 757 received 
placebo and 40 were randomly assigned but never started treatment. 784 patients 
in the MAGE-A3 group also received chemotherapy, as did 392 in the placebo 
group. Median follow-up was 38·1 months (IQR 27·9-48·4) in the MAGE-A3 group and 
39·5 months (27·9-50·4) in the placebo group. In the overall population, median 
disease-free survival was 60·5 months (95% CI 57·2-not reached) for the MAGE-A3 
immunotherapeutic group and 57·9 months (55·7-not reached) for the placebo group 
(hazard ratio [HR] 1·02, 95% CI 0·89-1·18; p=0·74). Of the patients who did not 
receive chemotherapy, median disease-free survival was 58·0 months (95% CI 
56·6-not reached) in those in the MAGE-A3 group and 56·9 months (44·4-not 
reached) in the placebo group (HR 0·97, 95% CI 0·80-1·18; p=0·76). Because of 
the absence of treatment effect, we could not identify a gene signature 
predictive of clinical benefit to MAGE-A3 immunotherapeutic. The frequency of 
grade 3 or worse adverse events was similar between treatment groups (246 [16%] 
of 1515 patients in the MAGE-A3 group and 122 [16%] of 757 in the placebo 
group). The most frequently reported grade 3 or higher adverse events were 
infections and infestations (37 [2%] in the MAGE-A3 group and 19 [3%] in the 
placebo group), vascular disorders (30 [2%] vs 17 [3%]), and neoplasm (benign, 
malignant, and unspecified (29 [2%] vs 16 [2%]).
INTERPRETATION: Adjuvant treatment with the MAGE-A3 immunotherapeutic did not 
increase disease-free survival compared with placebo in patients with 
MAGE-A3-positive surgically resected NSCLC. Based on our results, further 
development of the MAGE-A3 immunotherapeutic for use in NSCLC has been stopped.
FUNDING: GlaxoSmithKline Biologicals SA.