Pivotal Phase 3 Trial of Erlotinib in EGFR-Mutated NSCLC
The EURTAC trial is the pivotal phase 3 study of erlotinib in EGFR-mutated non-small cell lung cancer, demonstrating superior progression-free survival (9.7 months vs 5.2 months) compared to standard chemotherapy in European patients with EGFR mutations. 1
Key Trial Details
EURTAC (European Tarceva versus Chemotherapy) Trial:
- Design: Open-label, randomized phase 3 trial conducted at 42 hospitals in France, Italy, and Spain 1
- Population: 174 patients with advanced NSCLC harboring EGFR mutations (exon 19 deletion or L858R mutation in exon 21), chemotherapy-naïve for metastatic disease 1
- Intervention: Erlotinib 150 mg orally daily versus standard platinum-based chemotherapy (cisplatin 75 mg/m² plus docetaxel 75 mg/m² or gemcitabine 1250 mg/m²) 1
- Primary endpoint: Progression-free survival 1
Efficacy Results
The trial met its primary endpoint at interim analysis and enrollment was halted early due to clear superiority:
- Median PFS: 9.7 months (95% CI 8.4-12.3) with erlotinib versus 5.2 months (95% CI 4.5-5.8) with chemotherapy 1
- Hazard ratio: 0.37 (95% CI 0.25-0.54; p < 0.0001) 1
- Subgroup analysis by mutation type: HR for PFS was 0.27 in patients with exon 19 deletions and 0.52 in patients with exon 21 (L858R) substitution 2
Safety Profile
Erlotinib demonstrated a more favorable toxicity profile compared to chemotherapy:
- Grade 3-4 rash: 13% with erlotinib versus 0% with chemotherapy 1
- Grade 3-4 neutropenia: 0% with erlotinib versus 22% with chemotherapy 1
- Treatment-related severe adverse events: 6% with erlotinib versus 20% with chemotherapy 1
Supporting Trials
While EURTAC is the pivotal European trial, two other phase 3 trials support erlotinib's efficacy in EGFR-mutated NSCLC:
- OPTIMAL (CTONG-0802): Chinese trial showing erlotinib improved PFS compared to gemcitabine plus carboplatin in first-line treatment of EGFR mutation-positive patients 3, 4
- Study 1 (FDA registration trial): Demonstrated median PFS not reached versus 5.4 months with chemotherapy (HR 0.34, p < 0.001) 2
Clinical Implications
The EURTAC trial established erlotinib as a Category 1 first-line treatment option for EGFR-mutated NSCLC:
- Erlotinib is recommended as first-line therapy regardless of performance status, gender, tobacco exposure, or histology in patients with sensitizing EGFR mutations 3
- The trial strengthened the rationale for routine baseline tissue-based assessment of EGFR mutations in all patients with NSCLC 1
- Response rates with erlotinib in EGFR-mutated patients reach 65-67% compared to 16% with chemotherapy 3, 2
Important Caveats
Common pitfall: The SATURN trial 5 is sometimes confused as a pivotal trial, but it evaluated erlotinib as maintenance therapy after chemotherapy in unselected patients (not requiring EGFR mutations), showing only modest PFS benefit (12.3 vs 11.1 weeks, HR 0.71) 3, 5. This is distinct from first-line treatment of EGFR-mutated patients where erlotinib shows dramatic benefit 1.