A randomized placebo-controlled trial of erlotinib in patients with advanced non-small cell lung cancer (NSCLC) following failure of 1^st line or 2^nd line chemotherapy. A National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) trial

Abstract

7022 Background: In phase II studies, erlotinib has shown single agent activity in a number of tumor types, including NSCLC. NCIC CTG BR.21 is a randomized, placebo-controlled trial undertaken to determine if the Epidermal Growth Factor Receptor (EGFR) inhibitor erlotinib (Tarceva) prolongs survival in NSCLC patients after 1st or 2nd line chemotherapy. Methods: Eligibility criteria included stage IIIB/IV NSCLC, PS 0–3, 1–2 chemotherapy regimens (at least 1 combination regimen if < 70 yrs). Patients were stratified by center, PS (0,1 v 2,3), response to chemo (CR, PR v SD v PD), number of prior regimens (1 v 2), platinum (yes v no), and were randomized 2:1 to receive erlotinib 150 mg po/day or placebo. The 10 endpoint was survival with 20 endpoints of progression free survival (PFS), response, toxicity and QOL. Results: From Nov/01-Feb/03, 731 pts entered the study (median age 61y; 64% male; 67% PS 0,1). 50% had received 2 prior regimens, 93% had received platinum and 37% prior taxanes. Patient characteristics were well balanced. Overall response to erlotinib was 8.9% (95% CI: 6.6–12.0%, p < 0.001), median duration 34.2 wks. Statistically significant and clinically relevant differences were observed for overall survival and PFS. The planned primary QOL analysis, time to deterioration of patient reported symptoms (TTDS), showed statistically and clinically meaningful benefit for patients randomized to erlotinib. Rash and diarrhea were the most frequent symptoms; 5% of patients discontinued erlotinib for toxicity compared to 2% of patients on placebo. Conclusion: This is the first randomized trial to confirm that a Her1/EGFR inhibitor prolongs survival after 1st or 2nd line chemotherapy for NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration OSI Pharmaceuticals OSI Pharmaceuticals OSI Pharmaceuticals partially funded by a grant to the National Cancer Institute of Canada Clinical Trials Group from OSI Pharmaceuticals