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

doi:10.1016/j.clcc.2014.04.001

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 journal › Article › peer-review

24 Citations (Scopus)

Abstract

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 language	English
Pages (from-to)	156-163.e2
Number of pages	8
Journal	Clinical Colorectal Cancer
Volume	13
Issue number	3
DOIs	https://doi.org/10.1016/j.clcc.2014.04.001
Publication status	Published - 1 Sept 2014

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

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

Access to Document

10.1016/j.clcc.2014.04.001

Cite this

O'Neil, B., Cainap, C., Van Cutsem, E., Gorbunova, V., Karapetis, C., Berlin, J., Goldberg, R., Qin, Q., Qian, J., Ricker, J., Fischer, J., McKee, M., Carlson, D., & Kim, T. (2014). Randomized phase ii open-label study of mFOLFOX6 in combination with linifanib or bevacizumab for metastatic colorectal cancer. Clinical Colorectal Cancer, 13(3), 156-163.e2. https://doi.org/10.1016/j.clcc.2014.04.001

@article{7b9a1db593d9441eb3a08e873b30b80f,

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

abstract = "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.",

keywords = "ABT-869, Advanced colorectal cancer, Colon cancer, Second-line, TKI",

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

year = "2014",

month = sep,

day = "1",

doi = "10.1016/j.clcc.2014.04.001",

language = "English",

volume = "13",

pages = "156--163.e2",

journal = "Clinical Colorectal Cancer",

issn = "1533-0028",

publisher = "Elsevier Inc.",

number = "3",

}

O'Neil, B, Cainap, C, Van Cutsem, E, Gorbunova, V, Karapetis, C, Berlin, J, Goldberg, R, Qin, Q, Qian, J, Ricker, J, Fischer, J, McKee, M, Carlson, D & Kim, T 2014, 'Randomized phase ii open-label study of mFOLFOX6 in combination with linifanib or bevacizumab for metastatic colorectal cancer', Clinical Colorectal Cancer, vol. 13, no. 3, pp. 156-163.e2. https://doi.org/10.1016/j.clcc.2014.04.001

TY - JOUR

T1 - Randomized phase ii open-label study of mFOLFOX6 in combination with linifanib or bevacizumab for metastatic colorectal cancer

AU - O'Neil, Bert

AU - Cainap, Calin

AU - Van Cutsem, Eric

AU - Gorbunova, Vera

AU - Karapetis, Christos

AU - Berlin, Jordan

AU - Goldberg, Richard

AU - Qin, Qin

AU - Qian, Jiang

AU - Ricker, Justin

AU - Fischer, Judee

AU - McKee, Mark

AU - Carlson, Dawn

AU - Kim, Tae

PY - 2014/9/1

Y1 - 2014/9/1

N2 - 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.

AB - 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.

KW - ABT-869

KW - Advanced colorectal cancer

KW - Colon cancer

KW - Second-line

KW - TKI

UR - http://www.scopus.com/inward/record.url?scp=84908153722&partnerID=8YFLogxK

U2 - 10.1016/j.clcc.2014.04.001

DO - 10.1016/j.clcc.2014.04.001

M3 - Article

SN - 1533-0028

VL - 13

SP - 156-163.e2

JO - Clinical Colorectal Cancer

JF - Clinical Colorectal Cancer

IS - 3

ER -

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

Abstract

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Cite this