INTRODUCTION: This randomized phase II study investigated pemetrexed in 
combination with the epidermal growth factor receptor (EGFR)-targeting 
monoclonal antibody matuzumab compared with pemetrexed alone as second-line 
therapy for patients with advanced non-small cell lung cancer.
METHODS: Patients received pemetrexed 500 mg/m every 3 weeks either alone (n = 
50) or in combination with matuzumab at either 800 mg weekly (n = 51) or 1600 mg 
every 3 weeks (n = 47). The primary end point was objective response, as 
assessed by an independent review committee.
RESULTS: Tumor EGFR expression was detected in 87% of randomized patients. The 
objective response rate for the pooled matuzumab-treated arms was 11% compared 
with 5% for pemetrexed alone (p = 0.332). Apart from one patient in the 
pemetrexed alone group, all responses occurred in patients whose tumors 
expressed EGFR. The objective response rate for patients receiving weekly 
matuzumab was 16% compared with 2% for those receiving matuzumab every 3 weeks. 
There was also a trend for improved overall survival in patients receiving 
matuzumab weekly versus every 3 weeks (12.4 months versus 5.9 months, 
respectively, versus 7.9 months for pemetrexed alone). The combination of 
pemetrexed and matuzumab demonstrated an acceptable safety profile, with the 
most common grade 3/4 adverse event being neutropenia.
CONCLUSION: Although the analysis on the pooled matuzumab-treated arms did not 
demonstrate a statistically significant improvement in objective response for 
the addition of matuzumab to pemetrexed compared with pemetrexed alone, the 
trends for improvement in objective response and overall survival for pemetrexed 
plus weekly matuzumab compared with pemetrexed alone warrant confirmation in 
additional clinical trials.