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- Title
Multicenter Phase II Study of Tivozanib (AV-951) and Everolimus (RAD001) for Patients With Refractory, Metastatic Colorectal Cancer.
- Authors
Wolpin, Brian M.; Ng, Kimmie; Zhu, Andrew X.; Abrams, Thomas; Enzinger, Peter C.; McCleary, Nadine J.; Schrag, Deborah; Kwak, Eunice L.; Allen, Jill N.; Bhargava, Pankaj; Chan, Jennifer A.; Goessling, Wolfram; Blaszkowsky, Lawrence S.; Supko, Jeffrey G.; Elliot, Meaghan; Sato, Kaori; Regan, Eileen; Meyerhardt, Jeffrey A.; Fuchs, Charles S.
- Abstract
Background. Treatments that target the vascular endothelial growth factor (VEGF) pathway have efficacy in colorectal cancer. We evaluated tolerability and efficacy of tivozanib (an oral VEGF receptor-1, -2, -3 inhibitor) plus everolimus (an oral mammalian target of rapamycin inhibitor). Methods. The phase Ib study followed a 3 + 3 dose-escalation design with three dose levels. The primary objective in the follow-on phase II study was improvement in 2-month progression-free survival (PFS) from 30% (historical benchmark) to 50% in patients with refractory, metastatic colorectal cancer. Results. Dose-limiting toxicities in the phase Ib study were grade 3 fatigue and dehydration. Oral tivozanib (1 mg daily for 3 of 4 weeks) and oral everolimus (10 mg daily continuously) were advanced to a 40-patient phase II study. The most common grade 3-4 adverse events were thrombocytopenia and hypophosphatemia. The 2-month PFS rate was 50%, with 20 of 40 patients having stable disease (SD). Seven (18%) patients were treated for ≥6 months. Median PFS and overall survival (OS) times were 3.0 months (95% confidence interval [CI]: 1.9--3.6 months) and 5.6 months (95% CI: 4.4--10.6 months), respectively. Patients who developed grade 1hypertension had increased SD rates (65.2% vs. 29.4%) and longer OS times (10.6 vs. 3.7 months). Conclusions. The oral combination of tivozanib and everolimus was well tolerated, with stable disease achieved in 50% of patients with refractory, metastatic colorectal cancer.
- Subjects
ANTINEOPLASTIC agents; CLINICAL trials; COLON tumors; METASTASIS; RECTUM tumors; RAPAMYCIN; VASCULAR endothelial growth factors
- Publication
Oncologist, 2013, Vol 18, Issue 4, p377
- ISSN
1083-7159
- Publication type
Article
- DOI
10.1634/theoncologist.2012-0378