Efficacy of gemcitabine plus axitinib compared with gemcitabine alone in patients with advanced pancreatic cancer: an open-label randomised phase II study.
BACKGROUND
Axitinib (AG-013736) is a potent and selective oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, which have an important role in pancreatic cancer. The aim of this study was to assess the safety and efficacy of gemcitabine plus axitinib versus gemcitabine alone.


METHODS
Between January and August, 2006, 103 patients with unresectable, locally advanced, or metastatic pancreatic cancer were randomly assigned in a two to one ratio to receive gemcitabine (1000 mg/m(2)) plus axitinib 5 mg twice daily (n=69) or gemcitabine (1000 mg/m(2)) alone (n=34) by a centralised registration system. The primary endpoint was overall survival. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00219557.


RESULTS
All randomised patients were included in the efficacy analyses. Median overall survival was longer with gemcitabine plus axitinib than with gemcitabine alone (6.9 [95% CI 5.3-10.1] months vs 5.6 [3.9-8.8] months). The hazard ratio for survival with gemcitabine plus axitinib versus with gemcitabine alone, adjusted for stratification factors, was 0.71 (95% CI 0.44-1.13). The most common grade 3 or worse adverse events were fatigue (15 [22%] patients in the gemcitabine plus axitinib group vs one [3%] in the gemcitabine alone group), abdominal pain (eight [12%] vs five [16%]), and asthenia (eight [12%] vs one [3%]).


CONCLUSIONS
Gemcitabine plus axitinib showed a similar safety profile to gemcitabine alone; the small, non-statistically significant gain in overall survival needs to be assessed in a randomised phase III trial.
Spano
Jean-Philippe
JP
Hôpital de la Pitié Salpêtrière, Paris, France. jean-philippe.spano@psl.ap-hop-paris.fr
Chodkiewicz
Catherine
C
Maurel
Joan
J
Wong
Ralph
R
Wasan
Harpreet
H
Barone
Carlo
C
Létourneau
Richard
R
Bajetta
Emilio
E
Pithavala
Yazdi
Y
Bycott
Paul
P
Trask
Peter
P
Liau
Katherine
K
Ricart
Alejandro D
AD
Kim
Sinil
S
Rixe
Olivier
O
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D000077784:Axitinib; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007191:Indazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016016:Proportional Hazards Models; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D015996:Survival Rate; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D007093:Imidazoles; D007191:Indazoles; D003841:Deoxycytidine; D000077784:Axitinib; D040262:Receptors, Vascular Endothelial Growth Factor; D000093542:Gemcitabine