Efficacy report of a multicenter phase II trial testing a biologic-only combination of biweekly bevacizumab and daily erlotinib in patients with unresectable biliary cancer (BC): A Phase II Consortium (P2C) study

Abstract

4522 Background: Unresectable BCs, though uncommon, have a high mortality rate due to few effective available chemotherapies. BCs are known to express EGFR and increased angiogenesis in BC tumors has correlated with poor outcome. Bevacizumab (B), a VEGF inhibitor, and erlotinib (E), an EGFR tyrosine kinase inhibitor, have individually shown modest activity in BC (Philip et al, JCO 2006 and Clark et al, JCO 2007). The combination of B and E has demonstrated tolerability and modest efficacy in solid tumors (Hainsworth, et al, JCO 2005). Methods: Eligible patients have had no prior systemic treatment for metastatic or unresectable BC. Patients were treated with B 5 mg/kg IV d1,15 and E 150 mg PO QD d1–28, repeated every 28 days. The primary endpoint was confirmed response rate (RR). Two confirmed responses in 20 patients were required to complete enrollment of 50 patients, with 4 needed to declare efficacy (Fleming design). Secondary endpoints included tissue analysis for EGFR and signalling pathway member expresssion, EGFR mutation status, VEGF levels, and VEGFR-1 and -2 expression. Results: 34 eligible patients have been enrolled (13 male, 16/17/1 ECOG PS 0/1/2, 6 gallbladder, 27 cholangiocarcinoma). A median of 2 cycles have been administered (range 0–12), with 18 pts still on active treatment. 30 pts are evaluable for toxicity. One pt had grade 4 cerebral ischemia possibly related to treatment. Observed grade 3 events related to treatment included rash/desquamation (3), fatigue (1), hypokalemia (1), and hyponatremia (1). 1 pt died on day 21 of a CVA considered unrelated to treatment. 9 pts have progressed. Four partial responses have been observed in the first 20 evaluable pts (RR 20%, 95% 7–29%), lasting 3, 4, 6, and 9 mos. Seven patients had stable disease greater than 4 months duration. Conclusions: B and E is a tolerable regimen for BC. The RR observed warrants larger studies with greater than half the patients achieving a response or stable disease. Accrual continues to gain precision regarding study endpoints. Supported by the P2C Contract (NCI N01 CM62205). Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech Genentech