Artikel
Randomized Phase III trial of the multi-kinase inhibitor sorafenib (BAY 43-9006) in patients with advanced renal cell carcinoma (RCC)
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Autoren
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Michael Staehler
- Urologische Klinik der LMU München, Klinikum Grosshadern, Deutschland
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Bernard Escudier
- Institut Gustave Roussy, Villejuif, France
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C. Szczylik
- Military Institute of Medicine, Oncology Clinic, Warsaw
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T. Eisen
- Royal Marsden Hospital/Institute of Cancer Research
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S. Oudard
- Hospital Européen Georges Pompidou, Medical Oncology, Paris
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W.M. Stadler
- University of Chicago, Section of Hematology/Oncology, Chicago, IL 60637, United States
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B. Schwartz
- Bayer Pharmaceuticals Corporation, Westhaven, CT, United
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M. Shan
- Bayer Pharmaceuticals Corporation, Westhaven, CT, United
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R.M. Bukowski
- Cleveland Clinic Foundation, Cleveland. OH, United States
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BAY 43–9006 TARGETs Clinical Trial Group
| Veröffentlicht: | 20. März 2006 |
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Gliederung
Text
A phase II randomized discontinuation trial with the multi-kinase inhibitor sorafenib (BAY 43–9006) has shown significant efficacy against metastatic RCC.
The aim of this PhaseIII trial was to assess the effects of sorafenib (400 mg bid) versus placebo on overall survival (OS) as the primary endpoint and progression-free survival (PFS), best response (RECIST), patient reported outcome and adverse events (AEs) recorded by CTCAE v3.0 in advanced clear cell RCC patients (pts) after failing one prior systemic therapy. Pts were stratified by good or intermediate prognostic score (MSKCC) and country.
Baseline characteristics for all 903 pts were similar in both groups regarding mean age (59; 58 yrs. in sorafenib vs. placebo group), ECOG 0 (49%; 47%) and ECOG 1 (49%; 52%), Motzer prognostic factor low (52%; 50%) and intermediate score (48%; 50%), prior cytokine therapy (83%; 81%) and prior nephrectomy (94%; 93%). Drug-related AEs included diarrhea (43%; 13%), rash/desquamation (31%; 11%), hand–foot skin reaction (30%; 7%) and hypertension (17%; 2%). Fatigue (37%; 28%) was not markedly different between treatment groups. No relevant biochemical toxicity was observed. Median PFS was 5.5 months for sorafenib and 2.8 months for placebo (hazard ratio 0.51; p < 0.000001). The first planned interim analysis of OS after 220 events revealed a positive trend for the sorafenib group, which had not reached the median (>18 months), compared to the placebo group (14.7 months) with a hazard ratio of 0.72 (p=0.018). This difference did not reach statistical significance as the threshold for this analysis had been set to a=0.0005 (Fleming O´Brian design). The planned final analysis at 540 events will be performed with a preset a of ~0.04. The sorafenib treated patients showed in 76% tumor shrinkage and in 84% responses or stable disease. A statistically significant improvement of patient well being reported by the FACT-G and FACT-KSI-10 scores was seen for sorafenib. Plasma VEGF and soluble VEGFR levels may be potential biomarkers.
Sorafenib significantly prolongs PFS compared with placebo in pts with previously treated advanced RCC and shows a meaningful positive trend of increased OS in an interim analysis. Sorafenib is well tolerated with manageable side-effects.
