Randomized, Placebo-Controlled, Phase Ii Study of Sequential Erlotinib and Chemotherapy as First-Line Treatment for Advanced Non-Small-Cell Lung Cancer
Resource
JOURNAL OF CLINICAL ONCOLOGY v.27 n.30 pp.5080-5087
Journal
JOURNAL OF CLINICAL ONCOLOGY
Journal Volume
v.27
Journal Issue
n.30
Pages
5080-5087
Date Issued
2009
Date
2009
Author(s)
YU, CHONG-JEN
Abstract
Purpose This study investigated whether sequential administration of erlotinib and chemotherapy improves clinical outcomes versus chemotherapy alone in unselected, chemotherapy-naive patients with advanced non-small- cell lung cancer (NSCLC). Patients and Methods Previously untreated patients (n = 154) with stage IIIB or IV NSCLC and Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned to receive erlotinib (150 mg/d) or placebo on days 15 to 28 of a 4-week cycle that included gemcitabine (1,250 mg/m(2) days 1 and 8) and either cisplatin (75 mg/m2 day 1) or carboplatin (5 x area under the serum concentration-time curve, day 1). The primary end point was nonprogression rate (NPR) at 8 weeks. Secondary end points included tumor response rate, NPR at 16 weeks, duration of response, progression-free survival (PFS), overall survival (OS), and safety. Results The NPR at 8 weeks was 80.3% in the gemcitabine plus cisplatin or carboplatin (GC)-erlotinib arm (n = 76) and 76.9% in the GC- placebo arm (n = 78). At 16 weeks, the NPR was 64.5% for GC - erlotinib versus 53.8% for GC-placebo. The response rate was 35. 5% for GC-erlotinib versus 24.4% for GC-placebo. PFS was significantly longer with GC-erlotinib than with GC- placebo(adjusted hazard ratio, 0.47 ; log-rank P = .0002; median, 29.4 v 23.4 weeks); this benefit was consistent across all clinical subgroups. There was no significant difference in OS. The addition of erlotinib to chemotherapy was well tolerated, with no increase in hematologic toxicity , and no treatment- related interstitial lung disease. Conclusion Sequential administration of erlotinib following gemcitabine/platinum chemotherapy led to a significant improvement in PFS. This treatment approach warrants further investigation in a phase III study.
SDGs
Type
journal article