• Brian I Rini, Joaquim Bellmunt, Jill Clancy, Kongming Wang, Andreas G Niethammer, Subramanian Hariharan, and Bernard Escudier.
• Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Joaquim Bellmunt, University Hospital del Mar-IMIM, Barcelona, Spain; Jill Clancy, Kongming Wang, Andreas G. Niethammer, Subramanian Hariharan, Pfizer, New York, NY; and Bernard Escudier, Institut Gustave Roussy, Villejuif, France.
• J. Clin. Oncol. 2014 Mar 10; 32 (8): 752-9.

PurposeTo prospectively determine the efficacy of combination therapy with temsirolimus plus bevacizumab versus interferon alfa (IFN) plus bevacizumab in metastatic renal cell carcinoma (mRCC).Patients And MethodsIn a randomized, open-label, multicenter, phase III study, patients with previously untreated predominantly clear-cell mRCC were randomly assigned, stratified by prior nephrectomy and Memorial Sloan-Kettering Cancer Center prognostic group, to receive the combination of either temsirolimus (25 mg intravenously, weekly) or IFN (9 MIU subcutaneously thrice weekly) with bevacizumab (10 mg/kg intravenously, every 2 weeks). The primary end point was independently assessed progression-free survival (PFS).ResultsMedian PFS in patients treated with temsirolimus/bevacizumab (n = 400) versus IFN/bevacizumab (n = 391) was 9.1 and 9.3 months, respectively (hazard ratio [HR], 1.1; 95% CI, 0.9 to 1.3; P = .8). There were no significant differences in overall survival (25.8 ν 25.5 months; HR, 1.0; P = .6) or objective response rate (27.0% ν 27.4%) with temsirolimus/bevacizumab versus IFN/bevacizumab, respectively. Patients receiving temsirolimus/bevacizumab reported significantly higher overall mean scores in the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) -15 and FKSI-Disease Related Symptoms subscale compared with IFN/bevacizumab (indicating improvement); however, no differences in global health outcome measures were observed. Treatment-emergent all-causality grade ≥ 3 adverse events more common (P < .001) with temsirolimus/bevacizumab were mucosal inflammation, stomatitis, hypophosphatemia, hyperglycemia, and hypercholesterolemia, whereas neutropenia was more common with IFN/bevacizumab. Incidence of pneumonitis with temsirolimus/bevacizumab was 4.8%, mostly grade 1 or 2.ConclusionTemsirolimus/bevacizumab combination therapy was not superior to IFN/bevacizumab for first-line treatment in clear-cell mRCC.

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