Phase II trial of a non-platinum triplet for patients with advanced non-small cell lung carcinoma (NSCLC) overexpressing ERCC1 messenger RNA.

BACKGROUND: We prospectively evaluated the efficacy and toxicity of a non-platinum triplet regimen for patients with advanced non-small cell lung cancer (NSCLC) expected to be platinum-resistant.

METHODS: Patients were diagnosed with NSCLC using endobronchial ultrasonography with a guide sheath as a core biopsy. RNA was immediately isolated from unfixed biopsy specimens, and quantitative real-time reverse transcription-PCR assays were performed to determine ERCC1 messenger RNA expression. Patients with advanced, untreated NSCLC showing high ERCC1 levels (ΔCt ≧ 6.5) were assigned a non-platinum triplet regimen of irinotecan and paclitaxel plus bevacizumab. The primary end point was the objective response rate (ORR).

RESULTS: A total of 141 untreated patients were evaluated and 30 patients were entered into this phase II trial. The ORR was 66.7% (95% confidence interval [CI] 47.2-82.7) and median progression-free survival (PFS) was 215 days. Grade 4 thrombosis occurred in one patient, but other toxicities were mild and controllable. Fifty-six patients were treated with platinum-containing regimens and 24 patients responded (ORR 42.8%, 95% CI 29.7-56.7). Twenty-nine of these patients had high ERCC1 levels, of which 6 patients responded; 27 patients had low ERCC1 levels, 18 patients responded (P = 0.0053 by Fisher's exact test).

CONCLUSION: The triplet combination might be effective for patients with advanced, untreated NSCLC overexpressing ERCC1. ERCC1 messenger RNA levels may be a predictive factor for response to platinum-containing regimens.