A phase 2 study to evaluate the efficacy and safety of SU11248 in patients (pts) with unresectable neuroendocrine tumors (NETs)

Abstract

4008 Background: Standard cytotoxic chemotherapy has limited efficacy in pts with metastatic NETs. SU11248 is an oral multitargeted tyrosine kinase inhibitor with antiangiogenic and antitumor activity that specifically inhibits VEGFR, PDGFR, and c-KIT. NETs are known to be highly vascular, and both pancreatic NETs and carcinoid tumors have been shown to express high levels of both VEGF and VEGFR. In addition, evidence of clinical activity was seen in phase 1 studies. Methods: In this ongoing phase 2 study, pts with advanced, unresectable NETs were treated with repeated 6-wk cycles of SU11248, 50 mg po qd for 4 wks, followed by a 2-wk break. Treatment with prior cytotoxic chemotherapy was allowed, and pts receiving octreotide were allowed to continue treatment while on study. Pts were followed for adverse events, response, and overall survival. Pt-reported outcomes were compiled across four of the 6-week cycles using the EQ-5D and the FACIT-Fatigue subscale. Results: 106 pts were enrolled. Preliminary results are presented on 93 pts with the following characteristics: islet cell/carcinoid = 52/41; median age = 56 (range 32–81); M/F = 52/40; ECOG PS 0/1 = 50/41; prior systemic therapy: 53%; median days on treatment: 204 (range 26–543). Treatment-related toxicities were observed in 86 pts. Grade 3/4 toxicities included diarrhea (n=3, 3%), fatigue (n=23, 26%), glossodynia (n=3, 3%), nausea (n=6, 7%), neutropenia (n=12, 13%), thrombocytopenia (n=8, 9%), and vomiting (n=5, 6%). Other toxicities were infrequent. Response to therapy is shown in Table 1. There were no significant changes in quality of life over the first four treatment cycles. Conclusions: SU11248 is well tolerated and is associated with modest RRs and a high level of SD when used as a single agent in pts with advanced unresectable NET. Additional studies to explore the clinical benefit of SU11248 in pts with NET are warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Novartis, Pfizer, Sanofi Pfizer