| General information |
| Database: | DB00947 |
| Objective: | Bevacizumab or temsirolimus regimens have clinical activity in the firstline treatment of advanced renal cell carcinoma (RCC). Thisphase I/II trial was conducted to determine the safety of combining both agents and its efficacy in RCC patients who progressed on at least one prior antiVEGF receptor tyrosine kinase inhibitor (RTKI) agent |
| Authors: | Merchan JR, et al |
| Title: | Safety and activity of temsirolimus and bevacizumab in patients with advanced renal cell carcinoma previously treated with tyrosine kinase inhibitors: a phase 2 consortium study. |
| Journal: | Cancer Chemother Pharmacol. |
| Year: | 2015 |
| PMID: | 25556030 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | renal cell carcinoma |
| Cancer Subtype: | renal cell carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | temsirolimus + bevacizumab |
| Study Type: | phase I/II trial |
| Key Patients Feature: | advanced renal cell carcinoma patients who progressed on at least one prior antiVEGF receptor tyrosine kinase inhibitor (RTKI) agent. |
| Biomarker: | serum sFLT1 and VEGFA |
| Biomark Analysis: | Baseline levels of serum sFLT1 and VEGFA were inversely correlated with PFS and OS, respectively. |
| Control Group Info: | single arm |
| Treatment Info: | eligible patients were treated with temsirolimus (25 mg IV weekly) and escalating doses of IV bevacizumab (level 1 = 5 mg/kg; level 2 = 10 mg/kg) every other week. |
| Primary End Point: | the 6month progression free rate. |
| Secondary End Point: | response rate, toxicity evaluation, and PFS and OS. |
| Patients Number: | 12 |
| Trial Results |
| DLT_MTD: | Forty evaluable patients were treated with the phase II recommended dose (temsirolimus 25 mg IV weekly and bevacizumab 10 mg/kg IV every 2 weeks). |
| Objective Response Rate: | 23% |
| Disease Control Rate: | 85% |
| Median Time to Progression: | 7.6 (95% CI: 4.09.1) months |
| Median PFS A vs. C: | 5.9 (47.8) months |
| Median OS A vs. C: | 20.6 (11.523.7) months |
| Adverse Event(agent arm): | The most common (> 10% of subjects) adverse events (definitely, probable or possible attributed to study agents) for all (phase I and II) evaluable patients who received treatment (N=52) are shown in Table 2. The two most common grade 3 and 4 toxicities were hypertriglyceridemia (14%), fatigue and mucositis (10% each). Two patients (4%) developed intestinal perforation (grade 3) and two patients (4%) developed grade 3 bleeding. Thirtyone (of 52 evaluable) subjects required dose modification for Temsirolimus whereas six patients required holding or discontinuation of Bevacizumab due to toxicity. Patients who discontinued one agent could continue receiving the other study agent. A total of 9 patients (3 patients in the phase I portion, and 6 patients in the phase II portion) were removed from the study due to toxicity. |
| Conclusions: | Temsirolimus and bevacizumab is a feasible combination in patients with advanced RCC previously exposed to oral antiVEGF agents. The safety and efficacy results warrant further confirmatory studies in this patient population. |