Entry Detail
| General information | |
| Database: | DB00474 |
| Objective: | In the AXIS trial, axitinib prolonged progression free survival (PFS) vs sorafenib in patients with advanced renal cell carcinoma (RCC) previously treated with sunitinib or cytokines. |
| Authors: | Escudier B, et al |
| Title: | Axitinib versus sorafenib in advanced renal cell carcinoma: subanalyses by prior therapy from a randomisedphase III trial. |
| Journal: | Br J Cancer. |
| Year: | 2014 |
| PMID: | 24823696 |
| Trial Design | |
| Clinical Trial Id: | NCT00678392 |
| Agent: | axitinib |
| Target: | Macrophage colonystimulating factor 1 Vascular endothelial growth factor receptor 2 Plateletderived growth factor receptor |
| Cancer Type: | renal cell carcinoma |
| Cancer Subtype: | advanced clear cell renal carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | multicentre, openlabel, randomised, phase III trial |
| Key Patients Feature: | eligible patients had advanced RCC with clearcell histology, measureable disease per Response EvaluationCriteria in Solid Tumours (RECIST v1.0) (Therasse et al, 2000), Eastern Cooperative Oncology Group (ECOG) performance status0 or 1, and progressive disease after one prior sunitinib, bevacizumab plus interferonalfa, temsirolimus, or cytokinecontaining regimen. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | sorafenib |
| Treatment Info: | In post hoc analyses, patients were grouped by objective response to prior therapy (yes vs no), prior therapy duration (< vs median), and tumour burden (baseline sum of the longest diameter < vs median). |
| Primary End Point: | PFS and overall survival (OS), and safety by type and duration of prior therapy |
| Secondary End Point: | NA |
| Patients Number: | 723 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | When patients were grouped according to objective response to prior sunitinib or cytokine treatment, that is, complete or partial response vs stable or progressive disease, there were no statistically significant differences in PFS or OS in responders vs nonresponders treated with secondline axitinib or sorafenib |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | PFS was significantly longer in axitinibtreated patients who received longer prior cytokine treatment and sorafenibtreated patients with smaller tumour burden following sunitinib. |
| Median OS A vs. C: | From initiation of sunitinib treatment, median OS (95% confidence interval (CI)) was 33.7 months (28.6-36.9) in the axitinib arm vs 33.6 months (30.1-37.4) in the sorafenib arm (adjusted hazard ratio (HR) 1.019, 95% CI: 0.798-1.301; onesided P =0.560). From the start of cytokine treatment, median OS (95% CI) was 62.2 months (43.6-86.1) in the axitinib arm vs 55.8 months (35.0-212.1) in the sorafenib arm (adjusted HR 0.810, 95% CI: 0.553-1.186; onesided P = 0.139). |
| Adverse Event(agent arm): | Patients who received prior cytokines had a higher incidence (more than and equal to 5% difference) of grade more than and equal to 3 hypertension with secondline axitinib or sorafenib than those who received prior sunitinib. In sorafenibtreated patients, grademore than and equal to 3 hand-foot syndrome and increased lipase were also more frequently reported in the prior cytokine group. |
| Conclusions: | AXIS data suggest that longer duration of the firstline therapy generally yields better outcome with the secondline therapy and that lack of response to firstline therapy does not preclude positive clinical outcomes with a secondline vascular endothelial growth factortargeted agent in patients with advanced RCC. |