A controlled trial showed that axitinib plus gemcitabine did not improve outcomes in pancreatic cancer compared to gemcitabine alone.

Axitinib is a new inhibitor of vascular endothelial growth factor (VEGF) receptors that is in late-stage development. This trial investigated whether it was effective in the treatment of pancreatic cancer following promising results in early studies. Participants were adults with confirmed metastatic or locally-advanced pancreatic adenocarcinoma and adequate kidney, liver, and bone marrow function. They were randomised to treatment with gemcitabine plus axitinib or matching placebo, continued until disease progression, unacceptable adverse effects, or withdrawal of consent occurred. Primary outcome was overall survival, assessed after 460 deaths.

The trial was stopped early for futility by the data monitoring committee, after 230 deaths had occurred. Of 839 patients screened, 637 were randomised (316 to each treatment group): all except 2 in the axitinib group (data missing) were analysed for efficacy, however 19 did not receive the allocated treatment (11 axitinib, 8 placebo) and were not included in the safety analysis. At this point, there was no significant difference between the study groups in overall survival, which was 8.5 months (95% CI 6.9 to 9.5) for gemcitabine plus axitinib and 8.3 months (95% CI 6.9 to 10.3) for gemcitabine plus placebo (hazard ratio 1.014; 95% CI 0.786 to 1.309; one-sided p=0.5436).

Adverse effects were common in both groups, however asthenia, gastro-intestinal symptoms, dysphonia, and hypertension were more frequent in the axitinib group.

The authors conclude that adding axitinib to gemcitabine therapy does not improve outcomes in patients with advanced or metastatic pancreatic cancer. Their results are consistent with those of other trials involving VEGF inhibitors in pancreatic cancer, and suggest that VEGF inhibition is not an effective strategy in this disease.

An accompanying Comment discusses the future for treatment of pancreatic cancer. The author suggests criteria for future trials of potentially active drugs, and suggests that this trial of axitinib would not have fulfilled these.