Multicenter, randomized, phase II trial of CI-1033, an irreversible pan-ERBB inhibitor, for previously treated advanced non small-cell lung cancer.

Purpose: To evaluate the efficacy of the pan-ERBB inhibitor, CI-1033, in platinum-refractory or recurrent advanced-stage non-small-cell lung cancer (NSCLC).

Patients And Methods: This open-label, randomized phase II trial evaluated CI-1033 in patients with advanced-stage NSCLC who experienced treatment failure after or were refractory to platinum-based chemotherapy. Three oral CI-1033 doses were evaluated in 21-day dosing cycles: 50 mg daily for 21 consecutive days, 150 mg daily for 21 consecutive days, and 450 mg daily for 14 consecutive days followed by 7 days of no treatment. The primary efficacy end point was the 1-year survival rate.

Results: One hundred sixty-six patients were randomly assigned to treatment. Baseline patient demographics were well balanced. The most common drug-related adverse events were rash and diarrhea. The 450-mg arm (14 days on/7 days off) was closed early due to an excessive rate of adverse events. The 1-year survival rates were 29%, 26%, and 29%, respectively, in the three arms. The response rates were 2%, 2%, and 4%, and stable disease was confirmed in 16%, 23%, and 18% of patients, respectively, in the three study arms. Exploratory analyses demonstrated a prolonged survival in patients who developed a rash and in those with baseline tumor ERBB-2 expression.

Conclusion: CI-1033 had modest activity in unselected NSCLC patients but did not meet its primary end point. Future studies should focus on identifying methods of patient selection.