| General information |
| Database: | DB00498 |
| Objective: | They aimed to assess the potential synergistic or additive effect of the combination of bevacizumab, directed against the VEGF receptor, and temsirolimus, an mTOR inhibitor, in metastatic renal cell carcinoma. |
| Authors: | N¨¦grier S, et al |
| Title: | Temsirolimus and bevacizumab, or sunitinib, or interferon alfa and bevacizumab for patients with advanced renal cell carcinoma (TORAVA): a randomisedphase 2 trial. |
| Journal: | Lancet Oncol. |
| Year: | 2011 |
| PMID: | 21664867 |
| Trial Design |
| Clinical Trial Id: | NCT00619268 |
| Agent: | Temsirolimus and bevacizumab, or sunitinib, or interferon alfa and bevacizumab
|
| Target: | NA
|
| Cancer Type: | renal cell carcinoma |
| Cancer Subtype: | advanced renal cell carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 13 |
| Therapeutic Combination Content: | Temsirolimus + bevacizumab, or sunitinib, or interferon alfa + bevacizumab |
| Study Type: | an openlabel multicentre randomisedphase II trial |
| Key Patients Feature: | Patients aged 18 years or older who hadhistologically proven metastatic renal cell carcinoma ofany subtype except papillary carcinomas (which wereinvestigated in a concomitant specific trial; ClinicalTrials.gov number NCT00541008); an Eastern Cooperative Oncology Group (ECOG) performance status score of twoor less; no brain metastases; measurable metastases(Response Evaluation Criteria In Solid Tumors [RECIST]criteria20); liver, renal, and haematological functions in therange of 1.5 to two times above or below normal values;normal lipid and glycaemic concentrations; normalcardiac function within 6 weeks before randomisation;and no hyper tension were included. Other inclusioncriteria were no systemic treatment for the disease and nohistory of arterial or venous thrombosis in the past6 months. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | combination of bevacizumab (10 mg/kg every 2 weeks) and temsirolimus (25 mg weekly; group A), or one of the standard treatments: sunitinib (50 mg/day for 4 weeks followed by 2 weeks off; group B), or the combination of interferon alfa (9 mIU three times per week) and bevacizumab (10 mg/kg every 2 weeks; group C). |
| Treatment Info: | pts were randomly allocated in a 1:1 ratio to receive either comprehensive head and neck radiotherapy alone for 67 weeks or radiotherapy plus weekly doses of cetuximab: 400 mg/m(2) initial dose, followed by seven weekly doses at 250 mg/m(2). |
| Primary End Point: | progression free survival (PFS) at 48 weeks (four followup CT scans), which was expected to be above 50% in group A. |
| Secondary End Point: | NA |
| Patients Number: | 171 |
| Trial Results |
| DLT_MTD: | Grade 3 or worse adverse events werereported in 68 (77%) of 88 patients in group A versus 25 (60%) of 42 in group B and 28 (70%) of 40 in group C.Serious adverse events were reported in 39 (44%) of 88, 13 (31%) of 42, and 18 (45%) of 40 patients in groups A, B, and C, respectively. |
| Objective Response Rate: | PFS at 48 weeks was 29.5% (26 of 88 patients, 95% CI20.0-39.1) in group A, 35.7% (15 of 42, 21.2-50.2) in group B, and 61.0% (25 of 41, 46.0-75.9) in group C.Median PFS was 8.2 months (95% CI 7.0-9.6) in group A, 8.2 months (5.5-11.7) in group B, and 16.8 months(6.0-26.0) in group C. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median PFS was 8.2 months (95% CI 7.0-9.6) in group A, 8.2 months (5.5-11.7) in group B, and 16.8 months (6.0-26.0) in group C. |
| Median OS A vs. C: | 12month overall survival was 77% (95% CI 67-85), 74% (59-85), and 90% (77-96) in groups A, B, and C, respectively. |
| Adverse Event(agent arm): | Grade 3 or worse adverse events were reported in 68 (77%) of 88 patients in group A versus 25 (60%) of 42 in group B and 28 (70%) of 40 in group C. Serious adverse events were reported in 39 (44%) of 88, 13 (31%) of 42, and 18 (45%) of 40 patients in groups A, B, and C, respectively. |
| Conclusions: | The toxicity of the temsirolimus and bevacizumab combination was much higher than anticipated and limited treatment continuation over time. Clinical activity was low compared with the benefit expected from sequential use of each targeted therapy. This combination cannot be recommended for firstline treatment in patients with metastatic renal cell carcinoma. |