TY - JOUR
T1 - Efficacy and safety of axitinib in combination with gemcitabine in advanced pancreatic cancer
T2 - Subgroup analyses by region, including Japan, from the global randomized Phase III trial
AU - Ioka, Tatsuya
AU - Okusaka, Takuji
AU - Ohkawa, Shinichi
AU - Boku, Narikazu
AU - Sawaki, Akira
AU - Fujii, Yosuke
AU - Kamei, Yoichi
AU - Takahashi, Satori
AU - Namazu, Katsushi
AU - Umeyama, Yoshiko
AU - Bycott, Paul
AU - Furuse, Junji
N1 - Publisher Copyright:
© The Author 2015. Published by Oxford University Press.
PY - 2015/5/1
Y1 - 2015/5/1
N2 - Objective: Axitinib is a potent and selective inhibitor of vascular endothelial growth factor receptors 1-3. This analysis compared efficacy and safety of axitinib plus gemcitabine in patients with advanced pancreatic cancer from Japan, North America and the European Union, enrolled in a randomized Phase III study. Methods: Patients (n = 632), stratified by disease extent, were randomly assigned (1:1) to receive axitinib/gemcitabine or placebo/gemcitabine. Axitinib was administered at a starting dose of 5 mg orally twice daily and gemcitabine at 1000 mg/m2 once weekly for 3 weeks in 4 week cycles. Primary endpoint was overall survival. Results: Among Japanese patients, median overall survival was not estimable (95% confidence interval, 7.4 months-not estimable) with axitinib/gemcitabine (n = 58) and 9.9 months (95% confidence interval, 7.4-10.5) with placebo/gemcitabine (n = 56) (hazard ratio 1.093 [95% confidence interval, 0.525-2.274]). Median survival follow-up (range) was 5.1 months (0.02-12.3) with axitinib/gemcitabine vs. 5.4 months (1.8-10.5) with placebo/gemcitabine. Similarly, no difference was detected in overall survival between axitinib/gemcitabine and placebo/gemcitabine in patients from North America or the European Union. Common adverse events with axitinib/gemcitabine in Japanese patientswere fatigue, anorexia, dysphonia, nausea and decreased platelet count. Axitinib safety profile was generally similar in patients from the three regions, although there were differences in incidence of some adverse events. An exploratory analysis did not show any correlation between axitinib/gemcitabine-related hypertension and overall survival. Conclusions: Axitinib/gemcitabine, while tolerated, did not provide survival benefit over gemcitabine alone in patients with advanced pancreatic cancer from Japan or other regions.
AB - Objective: Axitinib is a potent and selective inhibitor of vascular endothelial growth factor receptors 1-3. This analysis compared efficacy and safety of axitinib plus gemcitabine in patients with advanced pancreatic cancer from Japan, North America and the European Union, enrolled in a randomized Phase III study. Methods: Patients (n = 632), stratified by disease extent, were randomly assigned (1:1) to receive axitinib/gemcitabine or placebo/gemcitabine. Axitinib was administered at a starting dose of 5 mg orally twice daily and gemcitabine at 1000 mg/m2 once weekly for 3 weeks in 4 week cycles. Primary endpoint was overall survival. Results: Among Japanese patients, median overall survival was not estimable (95% confidence interval, 7.4 months-not estimable) with axitinib/gemcitabine (n = 58) and 9.9 months (95% confidence interval, 7.4-10.5) with placebo/gemcitabine (n = 56) (hazard ratio 1.093 [95% confidence interval, 0.525-2.274]). Median survival follow-up (range) was 5.1 months (0.02-12.3) with axitinib/gemcitabine vs. 5.4 months (1.8-10.5) with placebo/gemcitabine. Similarly, no difference was detected in overall survival between axitinib/gemcitabine and placebo/gemcitabine in patients from North America or the European Union. Common adverse events with axitinib/gemcitabine in Japanese patientswere fatigue, anorexia, dysphonia, nausea and decreased platelet count. Axitinib safety profile was generally similar in patients from the three regions, although there were differences in incidence of some adverse events. An exploratory analysis did not show any correlation between axitinib/gemcitabine-related hypertension and overall survival. Conclusions: Axitinib/gemcitabine, while tolerated, did not provide survival benefit over gemcitabine alone in patients with advanced pancreatic cancer from Japan or other regions.
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U2 - 10.1093/jjco/hyv011
DO - 10.1093/jjco/hyv011
M3 - Article
C2 - 25647781
AN - SCOPUS:84930000609
SN - 0368-2811
VL - 45
SP - 439
EP - 448
JO - Japanese journal of clinical oncology
JF - Japanese journal of clinical oncology
IS - 5
ER -