Phase II study of dovitinib in patients progressing on anti-vascular endothelial growth factor therapy

Thomas Semrad, Edward Kim, Michael Tanaka, Jacob Sands, Chris Roberts, Rebekah A. Burich, Yu Li, David R Gandara, Primo N Lara, Philip Mack

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Background Prior work identified the fibroblast growth factor (FGF) pathway as a mediator of resistance to anti-vascular endothelial growth factor (VEGF) therapy. We tested dovitinib, an inhibitor of both FGF and VEGF receptors, in patients progressing on anti-VEGF treatment. Methods Patients with measurable advanced colorectal or non-small cell lung cancer with progression despite anti-VEGF treatment within 56 days, good performance status and adequate organ function were eligible. A research tumor biopsy was followed by treatment with dovitinib 500 mg on a 5-day on /2-day off schedule for 28-day cycles. The primary endpoint of tumor response was evaluated every 2 cycles. Secondary endpoints included toxicity and 8-week disease control rate. Intratumor mRNA expression of angiogenic mediators was analyzed using a next generation sequencing based expression array. Results Ten patients treated previously with bevacizumab or ziv-aflibercept enrolled. The study closed with termination of dovitinib development. No responses were observed in 7 evaluable patients. The best response was stable disease in 1 patient. Common toxicities included gastrointestinal, metabolic, and biochemical derangements. All patients experienced at least one grade ≥3 treatment-related adverse event, most commonly fatigue, elevated GGT, and lymphopenia. Expression of multiple angiogenic mediators was common in tumors progressing on anti-VEGF therapy including high levels of FGFR1 and VEGFA. Conclusions We found no evidence for the activity of dovitinib in patients who had recently progressed on anti-VEGF therapy and toxicities were significant. In tumors progressing despite anti-VEGF therapy, a multitude of pro-angiogenic mediators are expressed, including members of the FGF pathway.

Original languageEnglish (US)
Pages (from-to)21-26
Number of pages6
JournalCancer Treatment and Research Communications
Volume10
DOIs
StatePublished - Jan 1 2017

Keywords

  • Angiogenesis inhibitors
  • Dovitinib
  • Fibroblast growth factors
  • Vascular endothelial growth factors

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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