BACKGROUND: Necitumumab is a second-generation recombinant human immunoglobulin 
G1 EGFR monoclonal antibody that competitively inhibits ligand binding. We aimed 
to compare necitumumab plus pemetrexed and cisplatin with pemetrexed and 
cisplatin alone in patients with previously untreated, stage IV, non-squamous 
non-small-cell lung cancer (NSCLC).
METHODS: We did this randomised, open-label, controlled phase 3 study at 103 
sites in 20 countries. Patients aged 18 years or older, with an Eastern 
Cooperative Oncology Group (ECOG) performance status of 0-2 and adequate organ 
function, were randomly assigned 1:1 to treatment with a block randomisation 
scheme (block size of four) via a telephone-based interactive voice-response 
system or interactive web-response system. Patients received either cisplatin 75 
mg/m(2) and pemetrexed 500 mg/m(2) on day 1 of a 3-week cycle for a maximum of 
six cycles alone, or with necitumumab 800 mg on days 1 and 8. Necitumumab was 
continued after the end of chemotherapy until disease progression or 
unacceptable toxic effects. Randomisation was stratified by smoking history, 
ECOG performance status, disease histology, and geographical region. Patients 
and study investigators were not masked to group assignment. The primary 
endpoint was overall survival. Efficacy analyses were by intention to treat. 
This trial is registered with ClinicalTrials.gov, number NCT00982111.
FINDINGS: Between Nov 11, 2009, and Feb 2, 2011, we randomly assigned 633 
patients to receive either necitumumab plus pemetrexed and cisplatin (n=315) or 
pemetrexed and cisplatin alone (n=318). Enrolment was stopped on Feb 2, 2011, 
after a recommendation from the independent data monitoring committee. There was 
no significant difference in overall survival between treatment groups, with a 
median overall survival of 11·3 months (95% CI 9·5-13·4) in the necitumumab plus 
pemetrexed and cisplatin group versus 11·5 months (10·1-13·1) in the pemetrexed 
and cisplatin group (hazard ratio 1·01 [95% CI 0·84-1·21]; p=0·96). The 
incidence of grade 3 or worse adverse events, including deaths, was higher in 
the necitumumab plus pemetrexed and cisplatin group than in the pemetrexed and 
cisplatin group; in particular, deaths regarded as related to study drug were 
reported in 15 (5%) of 304 patients in the necitumumab group versus nine (3%) of 
312 patients in the pemetrexed and cisplatin group. Serious adverse events were 
likewise more frequent in the necitumumab plus pemetrexed and cisplatin group 
than in the pemetrexed and cisplatin group (155 [51%] of 304 vs 127 [41%] of 312 
patients). Patients in the necitumumab plus pemetrexed and cisplatin group had 
more grade 3-4 rash (45 [15%] of 304 vs one [<1%] of 312 patients in the 
pemetrexed and cisplatin alone group), hypomagnesaemia (23 [8%] vs seven [2%] 
patients), and grade 3 or higher venous thromboembolic events (23 [8%] vs 11 
[4%] patients) than did those in the pemetrexed and cisplatin alone group.
INTERPRETATION: Our findings show no evidence to suggest that the addition of 
necitumumab to pemetrexed and cisplatin increases survival of previously 
untreated patients with stage IV non-squamous NSCLC. Unless future studies 
identify potentially useful predictive biomarkers, necitumumab is unlikely to 
provide benefit in this patient population when combined with pemetrexed and 
cisplatin.
FUNDING: Eli Lilly and Company.