A multicenter phase II trial of adjuvant erlotinib in patients with resected non-small cell lung cancer (NSCLC) and mutations in the epidermal growth factor receptor (EGFR): Toxicity evaluation.

Abstract

7078 Background: Adjuvant chemotherapy for patients (pts) with resected NSCLC provides a modest survival benefit, but a large proportion of pts still relapse, presumably due to inherent chemoresistance. Tumors with activating EGFR mutations are exquisitely sensitive to the EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib; hence the use of adjuvant TKIs may more effectively prevent recurrences. This trial investigates the safety and efficacy of adjuvant erlotinib in pts with stage I-IIIA NSCLC and somatic EGFR mutations. Methods: Eligible pts have surgically resected stage IA-IIIA NSCLC and activating EGFR mutations. Within 6 months of surgery, and following the completion of routine adjuvant treatment, pts are treated with 150 mg/day of erlotinib for a total of 2 years, with surveillance scans every 6 months. The primary endpoint is disease-free survival at 2 years. Results: Thirty-six pts were enrolled at five sites between 1/08 and 11/09. Demographics include: stage I 53%; stage II 19%; stage IIIA 28%; female 75%; never-smokers 56%; exon 19 deletion 61%, L858R 36%. Significant toxicities are listed below (Table). 6 pts have been dose reduced to 100 mg/day and 4 additional pts to 50 mg/day for toxicities including rash, fatigue, diarrhea, transaminitis, and hyperbilirubinemia. 5 pts have withdrawn as a result of toxicity (n=3) or patient preference (n=2), mostly within the first month of treatment (n=4). Current average follow-up time is 8 months. Conclusions: Chronic treatment with adjuvant erlotinib in NSCLC pts with EGFR mutations is feasible. Major observed toxicities are consistent with those previously reported for erlotinib. Based the demonstrated role of EGFR TKIs in advanced NSCLC with EGFR mutations, this trial has been expanded to accrue 100 total patients. Toxicities Event Grade and frequency (%) I II III IV Total Rash 33 36 14 - 83 Diarrhea 58 3 3 - 64 Fatigue 31 17 6 - 53 Alopecia 19 11 - - 31 Nausea/vomiting 22 8 - - 31 Dry skin 25 - - - 25 Mucositis 17 3 - - 19 Pruritis 8 6 3 - 17 Skin erythema 11 6 - - 17 Ocular: dry eye, conjunctivitis 8 8 - - 17 Nail changes 14 - - - 14 AST/ALT 6 - 3 - 8 Bilirubin 3 3 - - 6 Pneumonitis - - - - 0 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, GlaxoSmithKline, OSI, Roche Genentech Genzyme