Axitinib plus gemcitabine versus placebo plus gemcitabine in patients with advanced pancreatic adenocarcinoma: A double-blind randomised phase 3 study
The Lancet Oncology, 02/10/2011
Clinical Article
Kindler HL et al. – The addition of axitinib to gemcitabine does not improve overall survival in advanced pancreatic cancer. These results add to increasing evidence that targeting of VEGF signalling is an ineffective strategy in this disease.
Methods- In this double-blind, placebo-controlled, phase 3 study, eligible patients had metastatic or locally advanced pancreatic adenocarcinoma, no uncontrolled hypertension or venous thrombosis, and Eastern Cooperative Oncology Group performance status 0 or 1
- Patients, stratified by disease extent (metastatic vs locally advanced), were randomly assigned (1:1) to receive gemcitabine 1000 mg/m2 intravenously on days 1, 8, and 15 every 28 days plus either axitinib or placebo
- Axitinib or placebo were administered orally with food at a starting dose of 5 mg twice a day, which could be dose-titrated up to 10 mg twice daily if well tolerated
- A centralised randomisation procedure was used to assign patients to each treatment group, with randomised permuted blocks within strata
- Patients, investigators, and the trial sponsor were masked to treatment assignments
- Primary endpoint OS
- All efficacy analyses done in all patients assigned to treatment groups for whom data available; safety and treatment administration and compliance assessments based on treatment received
- Between July 27, 2007, and Oct 31, 2008, 632 patients enrolled and assigned to treatment groups (316 axitinib, 316 placebo)
- At an interim analysis in January, 2009, independent data monitoring committee concluded that futility boundary had been crossed
- Median OS 8·5 months (95% CI 6·9—9·5) for gemcitabine plus axitinib (n=314, data missing for 2 patients) and 8·3 months (6·9—10·3) for gemcitabine plus placebo (n=316; HR 1·014, 95% CI 0·786—1·309; one-sided p=0·5436)
- Most common grade 3 or higher adverse events for gemcitabine plus axitinib and gemcitabine plus placebo hypertension (20 [7%] and 5 [2%] events, respectively), abdominal pain (20 [7%] and 17 [6%]), fatigue (27 [9%] and 21 [7%]), and anorexia (19 [6%] and 11 [4%])
