RECORD-2: phase II randomized study of everolimus and bevacizumab versus interferon alfa-2a and bevacizumab as first-line therapy in patients with metastatic renal cell carcinoma
Mené sur 365 patients atteints d'un carcinome métastatique à cellules rénales, cet essai de phase II compare l'efficacité, du point de vue de la survie sans progression, et la toxicité d'une combinaison évérolimus/bévacizumab et d'une combinaison interféron/bévacizumab en traitement de première ligne
Background : The open-label, phase II RECORD-2 trial compared efficacy and safety of first-line everolimus plus bevacizumab (EVE/BEV) with interferon plus bevacizumab (IFN/BEV) in patients with metastatic renal cell carcinoma (mRCC). Patients and methods : Previously untreated patients were randomized 1:1 to bevacizumab 10 mg/kg every 2 weeks with either everolimus 10 mg/day (EVE/BEV) or interferon (9 MIU 3 times/week, if tolerated) (IFN/BEV). Tumor assessments occurred every 12 weeks. Primary objective was the assessment of treatment effect on progression-free survival (PFS), based on an estimate of the chance of a subsequent phase III trial success (50% threshold for phase II success). Results : Baseline characteristics were balanced between the EVE/BEV (n=182) and IFN/BEV (n=183) arms. Median PFS was 9.3 and 10.0 months in the EVE/BEV and IFN/BEV arms, respectively (P=0.485). Predicted probability of phase III success was 5.05% (HR=0.91; 95% CI 0.69–1.19). Median duration of exposure was 8.5 and 8.3 months for EVE/BEV and IFN/BEV, respectively. Percentage of patients discontinuing because of adverse events (AEs) was 23.4% for EVE/BEV and 26.9% for IFN/BEV. Common grade 3/4 AEs included proteinuria (24.4%), stomatitis (10.6%), and anemia (10.6%) for EVE/BEV and fatigue (17.1%), asthenia (14.4%), and proteinuria (10.5%) for IFN/BEV. Median overall survival was 27.1 months in both arms. Conclusions : Efficacy of EVE/BEV and IFN/BEV appears similar. No new or unexpected safety findings were identified and, with the exception of proteinuria in about one-fourth of the population, EVE/BEV was generally well tolerated.