| General information |
| Database: | DB00503 |
| Objective: | To evaluate the efficacy and toxicity of the combination of bevacizumab, an angiogenesis inhibitor, and everolimus, an mTOR inhibitor, in the treatment of patients with advanced clear cell renal carcinoma. |
| Authors: | Hainsworth JD, et al |
| Title: | Phase II trial of bevacizumab and everolimus in patients with advanced renal cell carcinoma. |
| Journal: | J Clin Oncol. |
| Year: | 2010 |
| PMID: | 20368560 |
| Trial Design |
| Clinical Trial Id: | NCT00323739 |
| Agent: | bevacizumab and everolimus
|
| Target: | NA
|
| Cancer Type: | renal cell carcinoma |
| Cancer Subtype: | clear cell renal carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | bevacizumab + everolimus |
| Study Type: | multicenter, communitybasedphaseIItrial |
| Key Patients Feature: | Eligible patients were required to have biopsyproven metastatic or locally recurrent unresectable clear cell renal carcinoma (Fig 1). For mixedhistology tumors, the clear cell component had to comprise more than 75% ofthe biopsy specimen. patients were required to have nephrectomy more than30 days before initiating protocol therapy, except in situations in which extensive, symptomatic metastases precluded nephrectomy as a reasonable medicaloption. Patients in group A could not have received any previous targetedtherapy, whereaspatientsingroupBwererequiredtohaveexperienceddiseaseprogression on or been intolerant of previous therapy with sunitinib, sorafenib, or both. Previous treatment with a maximum of one immunotherapy, chemotherapy, or immunochemotherapy regimen for metastatic disease wasalsoallowedforpatientsinbothgroups |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | All patients received bevacizumab 10 mg/kg intravenously every 2 weeks and everolimus 10 mg orally daily. patients were evaluated for response after 8 weeks of treatment; patients with objective response or stable disease continued treatment until disease progression or unacceptable toxicity occurred. |
| Primary End Point: | PFS, OS and toxicities. |
| Secondary End Point: | NA |
| Patients Number: | 80 |
| Trial Results |
| DLT_MTD: | The most common grade 3 to 4toxicities included proteinuria (26%), mucositis/stomatitis (15%), fatigue (12%), and diarrhea (9%). |
| Objective Response Rate: | Fifteen (30%) of 50 patients (95%CI, 17.9% to 44.6%) without previous targeted therapy (group A) hadobjective responses to treatment (14 partial responses, one completeresponse). Thirtynine patients (78%) had measurable decrease intumor size, as shown in Figure 2A. Seven (23%) of 30 patients (95%CI, 9.9% to 42.3%) previously treated with sunitinib and/or sorafenibhad objective response (six partial responses, one complete response).In this group, a total of 22 patients (73%) had measurable tumorshrinkage |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median progression free survivals in previously untreated and previously treated patients were 9.1 and 7.1 months, respectively. |
| Median OS A vs. C: | Median OS for the entire group was 18.5 months (21.3 months for previously untreated patients, 14.5 months for previously treated patients; P .11). |
| Adverse Event(agent arm): | Grade 3 to 4 proteinuria was more frequent than expected (25%) and led to treatment discontinuation in six patients. |
| Conclusions: | Bevacizumabeverolimus is active and well tolerated in the treatment of advanced clear cell renal cancer, either as firstline treatment or after treatment with sunitinib andor sorafenib. The benefits of this combination regimen, versus sequential use of these two agents, requires further study. |