Sorafenib in Advanced Clear-Cell Renal-Cell Carcinoma
- Study type
- Clinical trial
- Study name
- TARGET
- Phase
- Phase 3
- Design
- Randomised, double-blind, placebo-controlled trial
- Sample size
- 903 patients
- Source
- N Engl J Med · 2007
- Trial registration
- NCT00073307
In plain words
In this study, the oral drug sorafenib was compared with a placebo (dummy pill) in patients with advanced kidney cancer in whom earlier treatments had not worked. Patients receiving sorafenib stayed longer without the disease growing (5.5 months versus 2.8 months). The drug caused side effects such as diarrhoea, skin rash, tiredness and skin reactions on the hands and feet, and sometimes also high blood pressure or heart problems.
Key results
Treatment arms and regimens
Sorafenib 400 mg (2 × 200 mg tablets) orally twice daily, continuously (451 patients); dose modification for toxicity was allowed.
452 patients; placebo. After the result of the planned progression-free survival analysis, crossover from placebo to sorafenib was allowed from May 2005.
Source of the regimen details: Abstract of the paper and ClinicalTrials.gov NCT00073307
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 unresectable or metastatic clear-cell renal cell carcinoma with measurable disease, who had received exactly one prior systemic therapy for advanced disease (mainly cytokines) and had completed it 30 days to 8 months before randomisation; ECOG 0 or 1; patients with rare subtypes (pure papillary, predominantly sarcomatoid, chromophobe etc.) or brain metastases were excluded. Enrolment from November 2003 to March 2005 (ClinicalTrials.gov).
Endpoints
Primary endpoint: overall survival. Progression-free survival was assessed in a planned analysis in January 2005. Treatment response and adverse events were also reported.
Safety and side effects
Diarrhoea, rash, fatigue and hand-foot skin reactions were the most common sorafenib-related adverse events. Hypertension and cardiac ischaemia were rare serious adverse events that were more common in the sorafenib group than in the placebo group. The rate of grade ≥3 adverse events is not given in the abstract.
Clinical significance and place in guidelines
According to the abstract, sorafenib increased progression-free survival in advanced clear-cell renal cell carcinoma after failure of prior therapy. A trend towards improved overall survival was seen at the interim analysis but did not meet the prespecified statistical threshold. Regulatory approval status and the current place of this drug in guidelines should be checked in up-to-date sources.
Limitations
The improvement in overall survival at the interim analysis was not significant under the O'Brien-Fleming boundary. After May 2005, crossover from placebo to sorafenib was allowed, which can make overall survival harder to interpret. Treatment was associated with increased toxic effects.
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.