Cetuximab and gemcitabine in elderly or adult PS2 patients with advanced non-small-cell lung cancer: The cetuximab in advanced lung cancer (CALC1-E and CALC1-PS2) randomized phase II trials.

Two parallel randomized phase 2 trials were performed to choose the optimal way of combining cetuximab with gemcitabine in the first-line treatment of elderly (CALC1-E) and adult PS2 (CALC1-PS2) patients with advanced NSCLC. METHODS: Stage IV or IIIB NSCLC patients, aged > or =70 years with PS 0-2 for CALC1-E or aged <70 with PS2 for CALC1-PS2, not selected for EGFR expression, were eligible. Patients were randomized to concomitant (gemcitabine, for a maximum of 6 cycles, plus cetuximab until progression) or sequential (gemcitabine, for a maximum of 6 cycles, followed by cetuximab) strategy. A selection design, with 1-year survival rate as the primary endpoint, was applied, requiring 58 elderly and 42 PS2 patients. RESULTS: All planned patients were randomized. In sequential arms, 34.5% and 60.0% patients were not able to receive cetuximab after gemcitabine in CALC1-E and CALC1-PS2, respectively. Survival rates (95% CI) at 1-year for concomitant and sequential arms were 41.4% (23.5-61.1) and 31.0% (15.3-50.8) in CALC1-E and 27.3% (10.7-50.2) and 35.0% (15.4-59.2) in CALC1-PS2. In both studies, survival curves crossed at about 10 months and the worse arm until that time became the better one at 1-year. Toxicity was similar across treatment groups. In concomitant arm of CALC1-E (but not of CALC1-PS2), survival was longer for patients who developed skin toxicity within the first two cycles of treatment. CONCLUSION: In both groups of patients, sequential strategy cannot be proposed for future trials because of low compliance. Inconsistency of survival outcomes makes also concomitant treatment not a candidate for further testing in unselected elderly and PS2 NSCLC patients.