Phase II trial of erlotinib in patients with advanced non‑small‑cell lung cancer harboring epidermal growth factor receptor mutations: additive analysis of pharmacokinetics.

Background: We conducted a phase II trial of erlotinib in patients with advanced non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations and evaluated the relationship between plasma concentration and efficacy of erlotinib.

Methods: Patients who were previously treated but naive to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), with advanced NSCLC harboring EGFR mutations, were enrolled. Erlotinib was given at 150 mg once daily until disease progression. The primary end point was objective response rate (ORR). Plasma trough levels of erlotinib were measured on Days 2 (D2) and 8 (D8) by high-performance liquid chromatography.

Results: In total, 29 patients were enrolled from September 2008 to January 2011. ORR was 61.5 % (95 % confidence interval [CI] 40.57–79.8) of 26 assessable patients. The median progression-free survival (PFS) and overall survival (OS) were 6.3 months and 16.9 months, respectively. Skin rash was observed in 24 patients, mostly at grade 1 or 2. Grade 2 pneumonitis was observed in one patient. We collected blood samples from 16 patients. The median PFS of the high and low D8/D2 ratio group was 11.2 months and 5.7 months, respectively (p = 0.044, hazard ratio = 0.301, 95 % CI 0.094–0.968).

Conclusion: Erlotinib showed an ORR comparable to that seen in previous studies for patients with NSCLC harboring EGFR mutations, although response, the primary end point, did not reach the predetermined threshold level. The D8/D2 ratio of erlotinib plasma trough levels might be a predictive factor for PFS.