Entry Detail
| General information | |
| Database: | DB00722 |
| Objective: | Axitinib is a potent, selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3. A randomisedphase 2 trial of gemcitabine with or without axitinib in advanced pancreatic cancer suggested increased overall survival in axitinibtreated patients. On the basis of these results, they aimed to assess the effect of treatment with gemcitabine plus axitinib on overall survival in a phase 3 trial. |
| Authors: | Kindler HL, et al |
| Title: | Axitinib plus gemcitabine versus placebo plus gemcitabine in patients with advanced pancreatic adenocarcinoma: a doubleblind randomisedphase 3 study. |
| Journal: | Lancet Oncol. |
| Year: | 2011 |
| PMID: | 21306953 |
| Trial Design | |
| Clinical Trial Id: | NCT00471146 |
| Agent: | axitinib |
| Target: | Macrophage colonystimulating factor 1 Vascular endothelial growth factor receptor 2 Plateletderived growth factor receptor |
| Cancer Type: | pancreatic cancer |
| Cancer Subtype: | pancreatic adenocarcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Axitinib plus gemcitabine |
| Study Type: | a phase III, randomised, doubleblind, global, multicentre, twogroup study |
| Key Patients Feature: | Eligible patients were at least18 years old with histologically or cytologically confirmedmetastatic or locally advanced pancreatic adenocarcinomanot amenable to curative resection. patients were requiredto have adequate bone marrow, hepatic, and renal function(including urine protein <2 g/24 h); an Eastern CooperativeOncology Group (ECOG) performance status of 0 or 1; andno uncontrolled hypertension (two baseline blood pressurereadings less than and equal to 140/90 mm Hg). |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | Axitinib plus gemcitabine VS placebo plus gemcitabine |
| Treatment Info: | Patients, stratified by disease extent (metastatic vs locally advanced), were randomly assigned (1:1) to receive gemcitabine 1000 mg/m(2) 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 dosetitrated up to 10 mg twice daily if well tolerated. |
| Primary End Point: | overall survival |
| Secondary End Point: | progression free survival, objective response rate, duration of response, safety, and health related quality of life |
| Patients Number: | 632 |
| Trial Results | |
| DLT_MTD: | The most common grade 3 or higher adverse events forgemcitabine plus axitinib and gemcitabine plus placebo were 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%]). |
| Objective Response Rate: | Median overall survival was 8.5 months (95% CI 6.9-9.5) for gemcitabineplus axitinib (n=314, data missing for two patients) and 8.3 months (6.9-10.3) for gemcitabine plus placebo (n=316;hazard ratio 1.014, 95% CI 0.786-1.309; onesided p=0.5436). |
| Disease Control Rate: | Axitinib plus gemcitabine: 30%; Placebo plus gemcitabine: 33%. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Axitinib plus gemcitabine: 4.4 (4.0-5.6) months; Placebo plus gemcitabine: 4.4 (3.7-5.2) months. Hazard ratio (95% CI):1.006 (0.779-1.298). P=0.5203.. |
| Median OS A vs. C: | 8.5 months (95% CI 6.9-9.5) for gemcitabine plus axitinib (n=314, data missing for two patients) and 8.3 months (6.9-10.3) for gemcitabine plus placebo (n=316; hazard ratio 1.014, 95% CI 0.786-1.309; onesided p=0.5436). |
| Adverse Event(agent arm): | The most common grade 3 or higher adverse events for gemcitabine plus axitinib and gemcitabine plus placebo were 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%]). |
| Conclusions: | 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. |