| General information |
| Database: | DB00130 |
| Objective: | To assess the efficacy of everolimus in patients with advanced hepatocellular carcinoma for whom sorafenib treatment failed. |
| Authors: | Zhu AX, et al |
| Title: | Effect of everolimus on survival in advanced hepatocellular carcinoma after failure of sorafenib: the EVOLVE1 randomized clinical trial. |
| Journal: | JAMA. |
| Year: | 2014 |
| PMID: | 25058218 |
| Trial Design |
| Clinical Trial Id: | NCT01035229. |
| Agent: | everolimus
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | liver cancer |
| Cancer Subtype: | advanced hepatocellular carcinoma failed after sorafenib |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a randomized, doubleblind, phase III study |
| Key Patients Feature: | adults with Barcelona Clinic Liver Cancer stage B or C hepatocellular carcinoma and ChildPugh A liver function whose disease progressed during or after sorafenib or who were intolerant of sorafenib. Patients were enrolled from 17 countries between May 2010 and March 2012. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | placebo |
| Treatment Info: | 7.5 mg/d, or matching placebo, both given in combination with best supportive care and continued until disease progression or intolerable toxicity. Per the 2:1 randomization scheme, |
| Primary End Point: | overall survival. |
| Secondary End Point: | time to progression and the disease control rate |
| Patients Number: | 546 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | disease control rate was 56.1% and 45.1%, respectively (P = .01). |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 3.0 months and 2.6 months, respectively (HR, 0.93; 95% CI, 0.751.15) |
| Median OS A vs. C: | 303 deaths (83.7%) in the everolimus group and 151 deaths (82.1%) in the placebo group ([HR], 1.05; 95% CI, 0.861.27; P = .68; median overall survival, 7.6 months with everolimus, 7.3 months with placebo). |
| Adverse Event(agent arm): | The most common grade 3/4 adverse events for everolimus vs placebo were anemia (7.8% vs 3.3%, respectively), asthenia (7.8% vs 5.5%, respectively), and decreased appetite (6.1% vs 0.5%, respectively). No patients experienced hepatitis C viral flare. Based on central laboratory results, hepatitis B viral reactivation was experienced by 39 patients (29 everolimus, 10 placebo); all cases were asymptomatic, but 3 everolimus recipients discontinued therapy. |
| Conclusions: | Everolimus did not improve overall survival in patients with advanced hepatocellular carcinoma whose disease progressed during or after receiving sorafenib or who were intolerant of sorafenib. |