Entry Detail
| General information | |
| Database: | DB00960 |
| Objective: | Currently, metastatic renal cell carcinoma is treated with sequential single agents targeting VEGF or mTOR. Here, they aimed to assess lenvatinib, everolimus, or their combination as secondline treatment in patients with metastatic renal cell carcinoma. |
| Authors: | Motzer RJ, et al |
| Title: | Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, openlabel, multicentre trial. |
| Journal: | Lancet Oncol |
| Year: | 2015 |
| PMID: | 26482279 |
| Trial Design | |
| Clinical Trial Id: | NCT01136733 |
| Agent: | lenvatinib |
| Target: | Alpha plateletderived growth factor receptor Mast/stem cell growth factor receptor Protooncogene tyrosineprotein kinase receptor ret VEGF receptor Fibroblast growth factor receptor |
| Cancer Type: | renal cell carcinoma |
| Cancer Subtype: | advanced renal cell carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | lenvatinib + everolimus |
| Study Type: | a randomised, phase II, openlabel, multicentre trial |
| Key Patients Feature: | patients with advanced or metastatic, clearcell, renal cell carcinoma;patients who had received treatment with a VEGFtargeted therapy and progressed on or within 9 months of stopping that agent. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | lenvatinib plus everolimus versus lenvatinib |
| Treatment Info: | patients were randomised via an interactive voice response system in a 1:1:1 ratio to either lenvatinib (24 mg/day), everolimus (10 mg/day), or lenvatinib plus everolimus (18 mg/day and 5 mg/day, respectively) administered orally in continuous 28day cycles until disease progression or unacceptable toxic effect |
| Primary End Point: | progression free survival in the intentiontotreat population. |
| Secondary End Point: | NA |
| Patients Number: | 153 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | 43% of patients allocated lenvatinib plus everolimus compared with 6% of who received singleagent everolimus (rate ratio [RR] 7.2, 95% CI 2.3-22.5; p<0.0001) and 27% of patients assigned singleagent lenvatinib (RR 1.6, 95% CI 0.9-2.8; p=0.10; singleagent lenvatinib vs singleagent everolimus, RR 4.5, 95% CI 1.4-14.7; p=0.0067 |
| Disease Control Rate: | 84% in Lenvatinib plus everolimus; 79% in Singleagent lenvatinib; 68% in Singleagent everolimus. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Lenvatinib plus everolimus significantly prolonged progression free survival compared with everolimus alone (median 14.6 months [95% CI 5.920.1] vs 5.5 months [3.57.1]; hazard ratio [HR] 0.40, 95% CI 0.240.68; p=0.0005), but not compared with lenvatinib alone (7.4 months [95% CI 5.610.2]; HR 0.66, 95% CI 0.301.10; p=0.12). |
| Median OS A vs. C: | 25.5 months (95% CI 20.8-25.5) for lenvatinib plus everolimus, 18.4 months (13.3-NE) for singleagent lenvatinib, and 17.5 months (11.8-NE) for singleagent everolimus. |
| Adverse Event(agent arm): | NA |
| Conclusions: | Lenvatinib plus everolimus and lenvatinib alone resulted in a progression free survival benefit for patients with metastatic renal cell carcinoma who have progressed after one previous VEGFtargeted therapy. Further study of lenvatinib is warranted in patients with metastatic renal cell carcinoma. |