Advanced (stage IIIb/IV) non-small cell lung cancers (NSCLCs) are associated with poor survival on current chemotherapy regimes. Epidermal growth factor receptor (EGFR)-directed tyrosine kinase inhibitors are second-line treatment options. This is the first study to investigate a monoclonal antibody against the EGFR cetuximab as a potential first-line treatment option.

In this multinational open-label study across 155 centres, 1125 chemotherapy-naïve patients with advanced NSCLC and immunohistochemical evidence of EGFR expression were randomly assigned to chemotherapy with cetuximab or chemotherapy alone. Patients previously treated with monoclonal antibodies or EGFR-targeting drugs were excluded. The primary outcome was overall survival. Secondary outcomes included progression-free survival, tumour response rate, safety and quality of life analyses.

On an intention-to-treat analysis, cetuximab therapy was associated with greater median survival than chemotherapy alone (11.3 vs.10.1 months), greater tumour response rates and a longer time to treatment failure. These findings were independent of histological subtype and other factors known to affect prognosis. No differences were reported between progression-free survival, quality of life outcomes or treatment-related deaths. Infusion reactions with cetuximab were rare.

The authors conclude that combination chemotherapy with cetuximab is a useful first-line therapy for advanced NSCLC. However, changes in symptom score and optimum duration of cetuximab treatment were not assessed. Unfortunately, it is likely that the benefit in overall survival compared with the cost of cetuximab treatment will be an issue in cetuximab becoming a first-line treatment option.

▸ Pirker R, Pereira JR, Szczesna A, et al and the FLEX Study Team. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomized phase III trial. Lancet 2009;373:1525–31.