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 - Bendell, Jc
AU - Tournigand, C
AU - Swieboda Sadlej, A
AU - Barone, Carlo Antonio
AU - Wainberg, Za
AU - Kim, Jg
AU - Pericay, C
AU - Pastorelli, D
AU - Tarazi, J
AU - Rosbrook, B
AU - Bloom, J
AU - Ricart, Ad
AU - Kim, S
AU - Sobrero, Af
PY - 2013
Y1 - 2013
N2 - This randomized phase II study evaluated axitinib or bevacizumab combined with chemotherapy in previously\r\ntreated patients with metastatic colorectal cancer. Survival was comparable with axitinib or bevacizumab\r\nwhen combined with second-line chemotherapy. Higher toxicity and treatment discontinuations due to adverse\r\nevents in axitinib arms suggest continuous dosing of axitinib plus chemotherapy may be less well tolerated\r\nthan bevacizumab plus chemotherapy.\r\nObjective: Axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors\r\n1, 2, and 3, shows activity in multiple tumor types, including those refractory to previous antiangiogenic therapy. This randomized,\r\nmulticenter, parallel-group, open-label phase II trial compared axitinib with bevacizumab each in combination with\r\n5-fluorouracil/leucovorin/oxaliplatin (FOLFOX) or 5-fluorouracil/leucovorin/irinotecan (FOLFIRI) for second-line treatment of\r\nmetastatic colorectal cancer. Methods: Patients were randomized 1:1 to axitinib 5 mg twice daily or bevacizumab 5 mg/kg\r\nevery 2 weeks plus modified FOLFOX-6 (if previously treated with irinotecan) or FOLFIRI (if previously treated with\r\noxaliplatin) and were stratified by performance status and prior bevacizumab therapy. Primary endpoint was progressionfree\r\nsurvival. Results: In 171 patients, progression-free survival was 7.6 months with axitinib/FOLFOX vs. 6.4 months with\r\nbevacizumab/FOLFOX (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.55-1.96; 1-sided P ¼ .55) and 5.7 months\r\nwith axitinib/FOLFIRI vs. 6.9 months with bevacizumab/FOLFIRI (HR, 1.27; 95% CI, 0.77-2.11; 1-sided P ¼ .83). Overall\r\nsurvival was 17.1 vs. 14.1 months with axitinib/FOLFOX and bevacizumab/FOLFOX (HR, 0.69; 95% CI, 0.37-1.27; 1-sided\r\nP 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\r\nP ¼ .88). More grade 3 adverse events (eg, diarrhea, fatigue, decreased appetite) and treatment discontinuations due to\r\nadverse events occurred with axitinib. Conclusions: Compared with bevacizumab, axitinib did not improve outcomes\r\nwhen added to second-line chemotherapy for metastatic colorectal cancer. With current dosing regimens, axitinib plus\r\nFOLFOX 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\r\ntreated patients with metastatic colorectal cancer. Survival was comparable with axitinib or bevacizumab\r\nwhen combined with second-line chemotherapy. Higher toxicity and treatment discontinuations due to adverse\r\nevents in axitinib arms suggest continuous dosing of axitinib plus chemotherapy may be less well tolerated\r\nthan bevacizumab plus chemotherapy.\r\nObjective: Axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors\r\n1, 2, and 3, shows activity in multiple tumor types, including those refractory to previous antiangiogenic therapy. This randomized,\r\nmulticenter, parallel-group, open-label phase II trial compared axitinib with bevacizumab each in combination with\r\n5-fluorouracil/leucovorin/oxaliplatin (FOLFOX) or 5-fluorouracil/leucovorin/irinotecan (FOLFIRI) for second-line treatment of\r\nmetastatic colorectal cancer. Methods: Patients were randomized 1:1 to axitinib 5 mg twice daily or bevacizumab 5 mg/kg\r\nevery 2 weeks plus modified FOLFOX-6 (if previously treated with irinotecan) or FOLFIRI (if previously treated with\r\noxaliplatin) and were stratified by performance status and prior bevacizumab therapy. Primary endpoint was progressionfree\r\nsurvival. Results: In 171 patients, progression-free survival was 7.6 months with axitinib/FOLFOX vs. 6.4 months with\r\nbevacizumab/FOLFOX (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.55-1.96; 1-sided P ¼ .55) and 5.7 months\r\nwith axitinib/FOLFIRI vs. 6.9 months with bevacizumab/FOLFIRI (HR, 1.27; 95% CI, 0.77-2.11; 1-sided P ¼ .83). Overall\r\nsurvival was 17.1 vs. 14.1 months with axitinib/FOLFOX and bevacizumab/FOLFOX (HR, 0.69; 95% CI, 0.37-1.27; 1-sided\r\nP 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\r\nP ¼ .88). More grade 3 adverse events (eg, diarrhea, fatigue, decreased appetite) and treatment discontinuations due to\r\nadverse events occurred with axitinib. Conclusions: Compared with bevacizumab, axitinib did not improve outcomes\r\nwhen added to second-line chemotherapy for metastatic colorectal cancer. With current dosing regimens, axitinib plus\r\nFOLFOX 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 - https://publicatt.unicatt.it/handle/10807/52409
UR - https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84887291388&origin=inward
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84887291388&origin=inward
U2 - 10.1016/j.clcc.2013.09.001
DO - 10.1016/j.clcc.2013.09.001
M3 - Article
SN - 1533-0028
VL - 12
SP - 239
EP - 247
JO - Clinical Colorectal Cancer
JF - Clinical Colorectal Cancer
IS - Dicembre
ER -