Bevacizumab plus erlotinib in patients (pts) with carcinoma of unknown primary site: A phase II trial of the Minnie Pearl Cancer Research Network

Abstract

3033 Background: Targeted therapies inhibiting tumor angiogenesis or the epidermal growth factor pathway have demonstrated efficacy in a variety of solid tumors. In this multicenter phase II trial, we evaluated the efficacy of combined targeted therapy with bevacizumab plus erlotinib in pts with carcinoma of unknown primary site. Methods: Eligibility criteria included: metastatic adenocarcinoma or poorly differentiated carcinoma of unknown primary site; 1 or 2 previous chemotherapy regimens (previously untreated pts were eligible only if considered poor candidates for chemotherapy due to advanced liver or bone metastases); measurable disease; ECOG PS 0–2; no previous anti-angiogenic or EGFR inhibitor therapy; no active brain metastases; no active thromboembolic disease or bleeding abnormalities; adequate organ function; informed consent. All pts received bevacizumab 10mg/kg IV q 2 weeks and erlotinib 150mg PO daily. Pts were evaluated for response after 8 weeks; treatment was continued until tumor progression. Results: 51 pts entered this clinical trial between 4/04 and 7/05. Pt characteristics: median age 57; male/female, 22/29; ECOG 0/1/2, 5/43/3; previous chemotherapy, 75%. 49 pts (96%) received at least 2 months therapy and were evaluable for response. Objective responses occurred in 4 pts (8%) (all ongoing at 5+ - 19+ months); 30 pts (59%) had stable disease/minor response. After median follow-up of 13 months, median progression-free survival for the entire group is 6.2 months. Median overall survival is 8.9 months, with 42% of pts alive at 1 year. 1-year survival for previously treated vs. untreated pts: 41% vs. 46%. Toxicity with this regimen was consistent with previous reports; other than fatigue (12%), no grade 3/4 toxicity was observed in > 10% of pts. Conclusions: The combination of bevacizumab and erlotinib has activity in pts with carcinoma of unknown primary site. Progression-free and overall survival results appear superior to our previous second-line results using a variety of chemotherapy regimens, and are similar to results with first-line chemotherapy. Future trials will evaluate bevacizumab/erlotinib as part of first-line therapy. [Table: see text]