A randomized, double-blind, phase III study comparing two doses of erlotinib for second-line treatment of current smokers with advanced non-small-cell lung cancer (CurrentS)

Objectives: Active smokers with non-small-cell lung cancer (NSCLC) have increased erlotinib metabolism versus non-smoking patients, which reduces exposure. Therefore, an increased erlotinib dose may be beneficial. The CurrentS study (NCT01183858) assessed efficacy and safety of 300 mg erlotinib (E300) as second-line therapy in current smokers with locally advanced or metastatic NSCLC versus the standard 150 mg dose (E150). Materials and methods: Patients with stage IIIB/IV NSCLC (current smokers who failed first-line platinum based chemotherapy) were randomized to receive E150 or E300 until progression/death/unacceptable toxicity. Primary endpoint: progression-free survival (PFS). Secondary endpoints: overall survival (OS), disease control rate and safety. Results: A total of 342 patients were screened; the intent-to-treat population comprised 159 E300 patients and 154 E150 patients. Median PFS was 7.0 versus 6.9 weeks with E300 versus E150, respectively (unstratified hazard ratio [HR] = 1.05, 95% confidence interval [CI]: 0.83-1.33; unstratified log-rank P = 0.671). Median OS was 6.8 months in both arms (unstratified HR = 1.03, 95% CI: 0.80-1.32; unstratified log-rank P = 0.846). Overall, 89.2% (E300 arm) and 84.4% (E150 arm) experienced >= 1 adverse event (AE) of any grade (44.3% and 37%, respectively, experienced grade >= 3 AEs); AEs of special interest were reported in 67.7% and 47.4% of patients, respectively. E300 resulted in higher mean plasma concentrations versus E150, however, this did not improve efficacy. Conclusions: Despite the difference in erlotinib exposure, there was no evidence of an incremental efficacy benefit of a higher erlotinib dose versus the standard dose in this population of highly active smokers. (C) 2016 Elsevier Ireland Ltd. All rights reserved.