Medical Oncology Unit, CHU Minjoz, Besançon, France
Antoine Thiery- Vuillemin , Aline Guillot , Thomas Steiner , Edwin Herrmann , Konstantinos N. Syrigos , Nadia Kelkouli , Agnese Cattaneo , Thierry Nguyen
Background: Everolimus is a mammalian target of rapamycin (mTOR) inhibitor. It gained approval based on the results of the RECORD-1 trial, which included patients with metastatic renal cell carcinoma (mRCC) whose disease progressed after receiving vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs). Bevacizumab is a monoclonal antibody targeting angiogenesis that is approved in patients (pts) with mRCC. AVATOR was the 1st study to explore the sequential use of bevacizumab followed by everolimus but with limited number of pts. Methods: In order to further explore this sequence pooled data from the AVATOR, CHANGE and TRAIN studies were analysed retrospectively. All pts had mRCC and were previously or currently treated with everolimus after failure of bevacizumab ± IFN. The primary end point was everolimus time to progression (TTP). Secondary end points were related to the overall survival (OS) of patients receiving the drug sequence, everolimus treatment and safety. Results: 89 pts were included in the analysis. Median age was 68 years [18-90]. At everolimus initiation ECOG was 0-1 for 72% pts and 16% were classified as poor prognosis from Heng classification. Exploring the duration of second-line everolimus treatment, 32% of patients received less than 3 months of everolimus and 35% received at least 6 months of treatment. At the time of data analysis, 20 pts (24%) were still receiving everolimus. Pts receiving everolimus after bevacizumab experienced a median TTP of 6 months [95%CI 4 - 14]. Median OS was not reached for everolimus second-line therapy. At 36 months after the start of first-line therapy, 60.4% of pts were still alive. All grades of common adverse events were consistent with the known safety profile of everolimus. Conclusions: The larger size of this cohort confirms the signal previously seen with AVATOR that the sequence of bevacizumab followed by everolimus displays interesting efficacy with not unexpected toxicity from everolimus and compares favourably with RECORD-1.
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