Randomized Phase II Open-Label Study of mFOLFOX6 in Combination With Linifanib or Bevacizumab for Metastatic Colorectal Cancer |
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| Affiliation: | 1. Vall d''Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona, Spain;2. Department of Comprehensive Cancer Care, Masarykuv Onkologicky Ustav, Brno, Czech Republic;3. Medical Clinic I, Prosper-Hospital, Recklinghausen;4. Department of Hematology/Oncology, Cancer Center Heilbronn-Franken, Heilbronn;5. Department of Oncology/Hematology, University Hospital Hamburg, Hamburg, Germany;6. Department of Digestive Oncology, University Hospital Gasthuisberg Leuven and KULeuven, Leuven, Belgium;7. Department of Oncology, Palacký University Medical School and Teaching Hospital, Olomouc;8. Department of Oncology, Horovice, Czech Republic;9. Department of Oncology, Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet, Szolnok, Hungary;10. GOU VPO St-Petersburg SMA, n/a Mechnikov Federal Agency of Healthcare, St Petersburg;11. City Clinical Oncology Dispensary, St Petersburg;12. S.I. Russian Cancer Research Center, Moscow, Russia;13. University Hospital Marques de Valdecilla, Santander, Spain;14. Merck KGaA, Darmstadt, Germany |
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| Abstract: | BackgroundAlthough 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 MethodsOne 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.ResultsNo 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.ConclusionCombining 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. |
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| Keywords: | ABT-869 Advanced colorectal cancer Colon cancer Second-line TKI |
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