Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial
- Study type
- Clinical trial
- Study name
- AVOREN
- Phase
- Phase 3
- Design
- Multicentre, randomised, double-blind (placebo-controlled) trial
- Sample size
- 649 patients
- Source
- The Lancet · 2007
In plain words
In this study, patients with kidney cancer that had spread and had not yet been treated received either the medicine bevacizumab with interferon or a placebo (dummy treatment) with interferon. Adding bevacizumab roughly doubled the time the disease stayed without getting worse (median 10.2 months versus 5.4 months). Tiredness and weakness were slightly more common in the bevacizumab group. The treating doctor should decide on the right treatment based on each patient's circumstances.
Key results
Treatment arms and regimens
Interferon alfa-2a 9 million IU subcutaneously three times a week + bevacizumab 10 mg/kg IV every 2 weeks (327 patients). Interferon dose reduction was allowed.
Placebo + interferon alfa-2a 9 million IU subcutaneously three times a week (322 patients).
Source of the regimen details: Abstract of the paper
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients with previously untreated metastatic renal cell carcinoma.
Endpoints
The primary endpoint was overall survival. Secondary endpoints included progression-free survival and safety. An interim analysis of overall survival was prespecified after 250 deaths. Because new second-line therapies became available during the trial, which could confound the overall survival analysis, it was agreed with regulatory authorities that the prespecified final analysis of progression-free survival was acceptable for regulatory submission. The protocol was amended to allow unblinding at this point. This paper reports the final analysis of progression-free survival. Efficacy analyses were by intention to treat.
Safety and side effects
325 patients in the bevacizumab + interferon group and 316 in the placebo + interferon group received at least one dose of study treatment. Deaths due to adverse events were reported in 8 patients (2%) who received one or more doses of bevacizumab and 7 patients (2%) who did not receive bevacizumab. Only 3 deaths in the bevacizumab group were considered by investigators to be possibly related to bevacizumab. The most common grade 3 or higher adverse events were fatigue in 40 patients (12%) versus 25 patients (8%) in the control group, and asthenia in 34 patients (10%) versus 20 patients (7%).
Clinical significance and place in guidelines
This trial showed that adding bevacizumab to interferon alfa in first-line treatment of metastatic renal cell carcinoma significantly improves progression-free survival. The abstract reports no conclusion on overall survival, because the final analysis of progression-free survival became the basis for regulatory submission. The status of this regimen in current clinical guidelines and its place relative to newer treatments should be checked in up-to-date guidelines.
Limitations
According to the abstract: the prespecified primary endpoint was overall survival, but because new second-line therapies became available, the final analysis of progression-free survival was reported and the study was unblinded at this point. The present report is the final analysis of progression-free survival.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.