Neuroendocrine tumors (NETs) are highly vascular neoplasms overexpressing vascular endothelial growth factor (VEGF) as well as VEGF receptors (VEGFR). Axitinib is a potent, selective inhibitor of VEGFR-1, -2 and -3, currently approved for the treatment of advanced renal cell carcinoma.
We performed an open-label, two-stage design, phase II trial of axitinib 5 mg twice daily in patients with progressive unresectable/metastatic low-to-intermediate grade carcinoid tumors. The primary endpoints were progression-free survival (PFS) and 12-month PFS rate. The secondary endpoints included time to treatment failure (TTF), overall survival (OS), overall radiographic response rate (ORR), biochemical response rate and safety. Thirty patients were enrolled and assessable for toxicity; 22 were assessable for response. After a median follow-up of 29 months, we observed a median PFS of 26.7 months (95% CI, 11.4-35.1), with a 12-month PFS rate of 74.5% (±10.2). The median OS was 45.3 months (95% CI, 24.4-45.3), and the median TTF was 9.6 months (95% CI, 5.5-12). Best radiographic response was partial response (PR) in 1/30 (3%) and stable disease (SD) in 21/30 patients (70%); 8/30 patients (27%) were unevaluable due to early withdrawal for toxicity. Hypertension was the most common toxicity and developed in 27 patients (90%). Grade 3/4 hypertension was recorded in 19 patients (63%), leading to treatment discontinuation in six patients (20%). Although axitinib appears to have an inhibitory effect on tumor growth in patients with advanced, progressive carcinoid tumors, the high rate of grade 3/4 hypertension may represent a potential impediment to its use in unselected patients.
Endocrine-related cancer. 2016 Apr 14 [Epub ahead of print]
Jonathan Strosberg, Mauro Cives, Jimmy Hwang, Thomas Weber, McKinley Nickerson, Chloe Atreya, Alan Venook, Katie Kelley, Tiffany Valone, Brian Morse, Domenico Coppola, Emily Bergsland
J Strosberg, GI Oncology, Moffitt Cancer Center, Tampa, 33612, United States., M Cives, GI Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, United States J Hwang, Department of Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, United States., T Weber, Department of Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, United States., M Nickerson, Department of Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, United States., C Atreya, Department of Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, United States., A Venook, Department of Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, United States., K Kelley, Department of Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, United States., T Valone, GI Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, United States., B Morse, Radiology, Moffitt Cancer Center, Tampa, United States., D Coppola, GI Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, United States., E Bergsland, Department of Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, United States.