Weekly and every 2 weeks cetuximab maintenance therapy after platinum-based chemotherapy plus cetuximab as first-line treatment for non-small cell lung cancer: randomized non-comparative phase IIIb NEXT trial.

The First-Line Erbitux in Lung Cancer (FLEX) trial showed that the addition of cetuximab to chemotherapy followed by weekly cetuximab maintenance significantly improved survival in the first-line treatment of advanced non-small cell lung cancer (NSCLC). The phase IIIb NSCLC Erbitux Trial (NEXT) trial (NCT00820755) investigated the efficacy and safety of weekly and every 2 weeks cetuximab maintenance therapy in this setting. Patients were treated with platinum-based chemotherapy plus cetuximab, and those progression-free after four to six cycles were randomized to every 2 weeks (500 mg/m(2)) or weekly (250 mg/m(2)) cetuximab maintenance. Randomization was stratified for tumor histology and response status. The primary endpoint for a regimen would be reached if the lower boundary of the 95 % confidence interval (CI) for the 1-year survival rate exceeded 55 %. A planned 480 patients were to be randomized. However, enrollment was curtailed following a negative opinion from the European Medicines Agency with regard to the use of cetuximab in this setting. After combination therapy, 311/583 (53.3 %) patients without progression were randomized to maintenance therapy: 157 to every 2 weeks cetuximab and 154 to weekly cetuximab. Baseline characteristics were balanced between these groups and exposure to cetuximab was similar. The 1-year survival rate was 62.8 % (95 % CI, 54.7-70.0) for every 2 weeks cetuximab and 64.4 % (95 % CI, 56.2-71.4) for weekly cetuximab. Safety profiles were similar, manageable, and in line with expectations. Therefore, in patients with advanced NSCLC who were progression-free after four to six cycles of first-line chemotherapy plus cetuximab, weekly and every 2 weeks cetuximab maintenance therapy were associated with similar survival outcomes.