TY - JOUR
T1 - Axitinib or bevacizumab plus FOLFIRI or modified FOLFOX-6 after failure of first-line therapy for metastatic colorectal cancer: a randomized phase II study
AU - Barone, Carlo Antonio
AU - Bendell, Johanna C.
AU - Tournigand, Christophe
AU - Swieboda-Sadlej, Anna
AU - Wainberg, Zev A.
AU - Kim, Jong Gwang
AU - Pericay, Carles
AU - Pastorelli, Davide
AU - Tarazi, Jamal
AU - Rosbrook, Brad
AU - Bloom, Joanna
AU - Ricart, Alejandro D.
AU - Kim, Sinil
AU - Sobrero, Alberto F.
PY - 2013
Y1 - 2013
N2 - This randomized phase II study evaluated axitinib or bevacizumab combined with chemotherapy in previously
treated patients with metastatic colorectal cancer. Survival was comparable with axitinib or bevacizumab
when combined with second-line chemotherapy. Higher toxicity and treatment discontinuations due to adverse
events in axitinib arms suggest continuous dosing of axitinib plus chemotherapy may be less well tolerated
than bevacizumab plus chemotherapy.
Objective: Axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors
1, 2, and 3, shows activity in multiple tumor types, including those refractory to previous antiangiogenic therapy. This randomized,
multicenter, parallel-group, open-label phase II trial compared axitinib with bevacizumab each in combination with
5-fluorouracil/leucovorin/oxaliplatin (FOLFOX) or 5-fluorouracil/leucovorin/irinotecan (FOLFIRI) for second-line treatment of
metastatic colorectal cancer. Methods: Patients were randomized 1:1 to axitinib 5 mg twice daily or bevacizumab 5 mg/kg
every 2 weeks plus modified FOLFOX-6 (if previously treated with irinotecan) or FOLFIRI (if previously treated with
oxaliplatin) and were stratified by performance status and prior bevacizumab therapy. Primary endpoint was progressionfree
survival. Results: In 171 patients, progression-free survival was 7.6 months with axitinib/FOLFOX vs. 6.4 months with
bevacizumab/FOLFOX (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.55-1.96; 1-sided P ¼ .55) and 5.7 months
with axitinib/FOLFIRI vs. 6.9 months with bevacizumab/FOLFIRI (HR, 1.27; 95% CI, 0.77-2.11; 1-sided P ¼ .83). Overall
survival was 17.1 vs. 14.1 months with axitinib/FOLFOX and bevacizumab/FOLFOX (HR, 0.69; 95% CI, 0.37-1.27; 1-sided
P ¼ .12) and 12.9 vs. 15.7 months with axitinib/FOLFIRI and bevacizumab/FOLFIRI (HR, 1.36; 95% CI, 0.82-2.24; 1-sided
P ¼ .88). More grade 3 adverse events (eg, diarrhea, fatigue, decreased appetite) and treatment discontinuations due to
adverse events occurred with axitinib. Conclusions: Compared with bevacizumab, axitinib did not improve outcomes
when added to second-line chemotherapy for metastatic colorectal cancer. With current dosing regimens, axitinib plus
FOLFOX or FOLFIRI seems to be less well tolerated than bevacizumab-based regimens.
AB - This randomized phase II study evaluated axitinib or bevacizumab combined with chemotherapy in previously
treated patients with metastatic colorectal cancer. Survival was comparable with axitinib or bevacizumab
when combined with second-line chemotherapy. Higher toxicity and treatment discontinuations due to adverse
events in axitinib arms suggest continuous dosing of axitinib plus chemotherapy may be less well tolerated
than bevacizumab plus chemotherapy.
Objective: Axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors
1, 2, and 3, shows activity in multiple tumor types, including those refractory to previous antiangiogenic therapy. This randomized,
multicenter, parallel-group, open-label phase II trial compared axitinib with bevacizumab each in combination with
5-fluorouracil/leucovorin/oxaliplatin (FOLFOX) or 5-fluorouracil/leucovorin/irinotecan (FOLFIRI) for second-line treatment of
metastatic colorectal cancer. Methods: Patients were randomized 1:1 to axitinib 5 mg twice daily or bevacizumab 5 mg/kg
every 2 weeks plus modified FOLFOX-6 (if previously treated with irinotecan) or FOLFIRI (if previously treated with
oxaliplatin) and were stratified by performance status and prior bevacizumab therapy. Primary endpoint was progressionfree
survival. Results: In 171 patients, progression-free survival was 7.6 months with axitinib/FOLFOX vs. 6.4 months with
bevacizumab/FOLFOX (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.55-1.96; 1-sided P ¼ .55) and 5.7 months
with axitinib/FOLFIRI vs. 6.9 months with bevacizumab/FOLFIRI (HR, 1.27; 95% CI, 0.77-2.11; 1-sided P ¼ .83). Overall
survival was 17.1 vs. 14.1 months with axitinib/FOLFOX and bevacizumab/FOLFOX (HR, 0.69; 95% CI, 0.37-1.27; 1-sided
P ¼ .12) and 12.9 vs. 15.7 months with axitinib/FOLFIRI and bevacizumab/FOLFIRI (HR, 1.36; 95% CI, 0.82-2.24; 1-sided
P ¼ .88). More grade 3 adverse events (eg, diarrhea, fatigue, decreased appetite) and treatment discontinuations due to
adverse events occurred with axitinib. Conclusions: Compared with bevacizumab, axitinib did not improve outcomes
when added to second-line chemotherapy for metastatic colorectal cancer. With current dosing regimens, axitinib plus
FOLFOX or FOLFIRI seems to be less well tolerated than bevacizumab-based regimens.
KW - Axitinib
KW - Chemotherapy
KW - Irinotecan
KW - Oxaliplatin
KW - Axitinib
KW - Chemotherapy
KW - Irinotecan
KW - Oxaliplatin
UR - http://hdl.handle.net/10807/52409
U2 - 10.1016/j.clcc.2013.09.001
DO - 10.1016/j.clcc.2013.09.001
M3 - Article
VL - 12
SP - 239
EP - 247
JO - Clinical Colorectal Cancer
JF - Clinical Colorectal Cancer
SN - 1533-0028
ER -