Randomized phase ii open-label study of mFOLFOX6 in combination with linifanib or bevacizumab for metastatic colorectal cancer

Bert O'Neil, Calin Cainap, Eric Van Cutsem, Vera Gorbunova, Christos Karapetis, Jordan Berlin, Richard Goldberg, Qin Qin, Jiang Qian, Justin Ricker, Judee Fischer, Mark McKee, Dawn Carlson, Tae Kim

    Research output: Contribution to journalArticlepeer-review

    20 Citations (Scopus)


    Background Although CRC is the third most commonly diagnosed cancer in the United States, second-line CRC treatment is limited. In this trial we examined the efficacy and safety of linifanib, an oral, potent, selective tyrosine kinase inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptor families, with mFOLFOX6, compared with bevacizumab and mFOLFOX6, in previously treated metastatic CRC.

    Patients and Methods One hundred forty-eight patients with advanced CRC previously treated with fluoropyrimidine or irinotecan received bevacizumab (10 mg/kg, intravenous), low-dose linifanib (7.5 mg), or high-dose linifanib (12.5 mg), with mFOLFOX6. The primary end point was progression-free survival (PFS). Secondary objectives included overall survival (OS), objective response rate (ORR), and safety.

    Conclusion Combining linifanib with mFOLFOX6 as a second-line treatment for metastatic CRC did not improve PFS, radiographic findings, or duration of response versus bevacizumab and mFOLFOX6.

    Results No statistically significant differences in PFS occurred between bevacizumab and linifanib doses (low, hazard ratio [HR], 1.453 [95% confidence interval [CI], 0.830-2.539]; high, HR, 1.257 [95% CI, 0.672-2.351]). Median OS values were similar for bevacizumab and high-dose linifanib (bevacizumab, 16.5 months [95% CI, 13.0-not available]; high-dose linifanib, 16.4 months [95% CI, 11.9-21.7]; low-dose linifanib, 12.0 months [95% CI, 10.1-13.0]). ORRs were similar (bevacizumab, 34.7% [95% CI, 21.7-49.6]; low-dose linifanib, 24.0% [95% CI, 13.1-38.2]; high-dose linifanib, 22.4% [95% CI, 11.8-36.6]). Median cycles of 5-fluorouracil were reduced in the linifanib arms, versus the bevacizumab arm. Grade 3/4 adverse event occurrences were more frequent with linifanib. Palmar-plantar erythrodysesthesia, hypothyroidism, and thrombocytopenia were more common with high-dose linifanib than bevacizumab.

    Original languageEnglish
    Pages (from-to)156-163.e2
    Number of pages8
    JournalClinical Colorectal Cancer
    Issue number3
    Publication statusPublished - 1 Sep 2014


    • ABT-869
    • Advanced colorectal cancer
    • Colon cancer
    • Second-line
    • TKI


    Dive into the research topics of 'Randomized phase ii open-label study of mFOLFOX6 in combination with linifanib or bevacizumab for metastatic colorectal cancer'. Together they form a unique fingerprint.

    Cite this