| General information |
| Database: | DB00508 |
| Objective: | They did a phase III, randomised, doubleblind, placebocontrolled trial of everolimus in patients with metastatic renal cell carcinoma whose disease had progressed on vascular endothelial growth factortargeted therapy. |
| Authors: | Motzer RJ, et al |
| Title: | Efficacy of everolimus in advanced renal cell carcinoma: a doubleblind, randomised, placebocontrolledphase III trial. |
| Journal: | Lancet. |
| Year: | 2008 |
| PMID: | 18653228 |
| Trial Design |
| Clinical Trial Id: | NCT00410124 |
| Agent: | everolimus
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | renal cell carcinoma |
| Cancer Subtype: | advanced renal cell carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a doubleblind, randomised, placebocontrolledphase III trial |
| Key Patients Feature: | he study populationconsisted of adults (aged 18 years and above) withmetastatic renal cell carcinoma that showed a clearcellcomponent, which had progressed on or within6 months of stopping treatment with sunitinib orsorafenib, or both drugs. Previous therapy withbevacizumab, interleukin 2, or interferon alfa was alsopermitted. Key eligibility criteria included the presenceof measurable disease (as per the Response Evaluation Criteria in Solid Tumours [RECIST]16), a Karnofskyperformance status score of 70% or more (on a scaleof 0 to 100, with higher scores indicating betterperformance), and adequate bone marrow, hepatic, andrenal function. Patients were ineligible if they hadpreviously received mTOR inhibitor therapy(temsirolimus), had untreated CNS metastases, oruncontrolled medical conditions (eg, unstable anginapectoris, symptomatic congestive heart failure, recentmyocardial infarction, or diabetes). |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | A:everolimus B:placebo |
| Treatment Info: | pts were randomly assigned in a two to one ratio to receive everolimus 10 mg once daily (n=272) or placebo (n=138), in conjunction with best supportive care. Randomisation was done centrally via an interactive voice response system using a validated computer system, and was stratified. |
| Primary End Point: | progression free survival; |
| Secondary End Point: | safety, objective tumour response rate, overall survival, diseaserelated symptoms, and qualityoflife |
| Patients Number: | 410 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Confirmed objective tumour responses (all partialresponses) assessed by independent central review wereseen in three (1%) patients receiving everolimus andnone in the placebo group |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 4.0 [95% CI 3.7-5.5] vs 1.9 [1.8-1.9] months). |
| Median OS A vs. C: | median overall survival had not been reached for the everolimus group and was 8.8 (95% CI 7.9-not available) months for the placebo group. |
| Adverse Event(agent arm): | Stomatitis (107 [40%] patients in the everolimus group vs 11 [8%] in the placebo group), rash (66 [25%] vs six [4%]), and fatigue (53 [20%] vs 22 [16%]) were the most commonly reported adverse events, but were mostly mild or moderate in severity. Pneumonitis (any grade) was detected in 22 (8%) patients in the everolimus group, of whom eight had pneumonitis of grade 3 severity. |
| Conclusions: | Treatment with everolimus prolongs progression free survival relative to placebo in patients with metastatic renal cell carcinoma that had progressed on other targeted therapies. |