The evidence supporting this regimen comes from a multicentre, randomised phase lll trial, reported by Motzer et al.r Between December 2006 and October 2007, 410 patients, with metastatic renal cell carcinoma with clear cell histology who had progressed on or within 6 months of stopping treatment with sunitinib or sorafenib, or both drugs, were randomised to receive everolimus 10 mg once daily (n=272) or placebo (n=138), in conjunction with best supportive care. Patients who had previously received temsirolimus were excluded from the trial.
The primary end point was progression free survival. Secondary endpoints were overall survival, safety, best response rate and quality of life. Cross over after the cut-off date was allowed for patients who progressed on placebo.
All randomised patients were included in efficacy analyses. The results of the second interim analysis indicated a significant difference in efficacy between arms and the trial was thus halted early after 191 progression events had been observed. 101 (37%) events occurred in the everolimus group and 90 (65%) events in the placebo group (HR= 0.30; p<0.0001) The median progression-free survival at the time of analyses was 4.0 vs 1.9 months.r
The final results reported the median progression-free survival 4.9 vs 1.9 months (HR 0.33; p<0.001). The median overall survival was 14.8 vs. 14.4 months for everolimus and placebo (HR 0.87; p=0.162). At the time of the final analysis, 80% of patients in the placebo arm had crossed over to the open-label everolimus. Independent prognostic factors for shorter OS in the study included low performance status, high corrected calcium, low haemoglobin, and prior sunitinib (p<0.01).r
Kaplan-Meier estimates of progression-free survivalr
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Stomatitis, diarrhoea, rash and fatigue were the most commonly reported adverse events, but were mostly mild or moderate in severity. Pneumonitis (any grade) was detected in 37 (14%) patients in the everolimus group, of whom 4% had pneumonitis of grade 3 severity.
During the double-blinded period, 4 patients died from causes other than disease progression; 3 were infection related and 1 with acute respiratory failure with disease progression, this patient having grade 3 everolimus related pulmonary toxicity.r
Treatment-related adverse events occurring in at least 10% of patientsr
© Cancer 2010