A phase I study of erlotinib and bevacizumab for recurrent or metastatic squamous cell carcinoma of the head and neck (HNC)

Abstract

5504 Background: We previously reported single agent activity for gefitinib in HNC (Cohen, JCO, 2003). EGFR activation can upregulate vascular endothelial growth factor (VEGF) which has been correlated with resistance to anti-EGFR agents. Therefore, we conducted a phase I-II study of the oral EGFR tyrosine kinase inhibitor (TKI), erlotinib with the monoclonal VEGF antibody, bevacizumab. Methods: Phase I trial at fixed dose of erlotinib 150 mg orally PO daily with escalation of bevacizumab to a maximum of 15 mg/kg q 3 weeks (Mauer, PASCO, 2003). During phase II, a two-stage accrual design was applied. Eligible pts had metastatic and/or recurrent incurable HNC with up to 1 prior chemotherapy regimen for recurrent disease, no prior EGFR or VEGF-based therapy, performance status > 60%, and normal organ and bone marrow function. Pts were excluded for tumors close to or encasing a major vessel, and a history of bleeding diathesis. Pts were randomized to receive the initial bevacizumab dose on either day 15 or day 1 of a daily schedule of erlotinib administration. Subsequent doses of bevacizumab were administered every 21 days. Results: Between 3/03 and 11/04, a total of 51 pts were entered; male, 76%, median age 58 (39–81), performance status 0: 14 pts, 1: 34 pts, and 2: 3 pts. 86% of pts had received prior chemotherapy. No dose limiting toxicities were observed during phase I. A total of 45 pts were treated at the phase II dose of erlotinib 150 mg PO daily and bevacizumab 15 mg/kg q 3 weeks. Cycle number ranged from 1–10. Toxicities include skin rash in 28 of 44 currently evaluated pts (grade 1: 18, grade 2: 10), diarrhea in 15 pts (grade 1: 10, grade 2: 3, grade 3: 2 pts); fatigue in 21 pts, and grade 4 hemorrhage in 1 pt. Best response is CR: 2 pt; PR: 3 pts; SD: 31 pts; PD: 11 pts, and too early: 4 pts. At the time of this analysis, a total of 30 pts have progressed or died. Median progression-free survival is 127 days (95% CI: 85 - 151 days); overall survival is 226 days. Conclusions: The combination of erlotinib and bevacizumab is well tolerated at the doses utilized in this study. The observed response/stable disease rate is encouraging. Mature data on TTP and OS will be available. (supported by NIH N01 CM-17102–01) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Genentech/OSI Genentech Genentech/OSI NCI