A multicenter phase II study of erlotinib and bevacizumab in patients with metastatic melanoma

Abstract

8539 Background: Erlotinib and bevacizumab have demonstrated activity in a number of malignancies by virtue of interrupting interdependent signaling pathways thought important in tumorigenesis. Melanoma may be an appropriate target based on its expression of EGFR and VEGF. We conducted a phase II multi-institutional trial evaluating erlotinib and bevacizumab in advanced melanoma patients. Methods: Eligibility included measurable disease, ECOG PS = 0–1, adequate organ function, no more than one prior therapy for metastatic disease, and CNS metastases were allowed if limited and controlled. Patients received oral erlotinib 150 mg/day and bevacizumab 10 mg/kg IV Q 2 weeks with tumor evaluation every 8 weeks. The primary outcomes were response rate (RR), response duration, and frequency of PFS >6 months. Secondary outcomes included overall survival, safety, and tolerability. A two-stage accrual design was employed ensuring that = 3/21 patients had PFS >6 months before additional patients were accrued. Results: As of Nov 2006, 29 patients with metastatic melanoma were enrolled. A total of 23 patients were evaluable for response. The majority was male 19/29 (65%) and had a median age = 62 yrs (range 35–78 years). Fifteen of the 29 had stage M1c disease (51.7%) and 18/29 (62.1%) had a PS = 1. Ten patients (34%) had prior adjuvant therapy and 6 patients (21%) prior therapy for metastatic disease. There were 2/23 (9%) partial responses lasting < 6 months and 5/23 (22%) had stable disease lasting > 6 months. The median progression free survival of evaluable patients was 96 days (95% CI: 50 - 142 days). A total of 25 grade III toxicities were observed with the most common being rash/pruritis (n=4), pain (n=4), fatigue (n=3), hypertension (n=2) and diarrhea (n=2). Two grade IV toxicities were observed (myocardial infarction and bowel perforation) both thought to be due to bevacizumab. Conclusion: The combination of erlotinib (150 mg/day) and bevacizumab (10 mg/kg) appears potentially active in patients with metastatic melanoma with largely tolerable toxicities. Accrual of a total of 41 patients will be completed shortly. [Table: see text]