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Ref Type | Journal Article | ||||||||||||
PMID | (28832978) | ||||||||||||
Authors | Dorff TB, Longmate JA, Pal SK, Stadler WM, Fishman MN, Vaishampayan UN, Rao A, Pinksi JK, Hu JS, Quinn DI, Lara PN | ||||||||||||
Title | Bevacizumab alone or in combination with TRC105 for patients with refractory metastatic renal cell cancer. | ||||||||||||
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Abstract Text | Targeting the vascular endothelial growth factor (VEGF) pathway has improved outcomes in metastatic renal cell carcinoma (RCC); however, resistance inevitably occurs. CD105 (endoglin) is an angiogenic pathway that is strongly upregulated after VEGF inhibition, potentially contributing to resistance. The authors tested whether TRC105, a monoclonal antibody against endoglin, impacted disease control in patients with previously treated RCC who were receiving bevacizumab.Eligible patients with metastatic RCC who had previously received 1 to 4 prior lines of therapy, including VEGF-targeted agents, were randomized 1:1 to receive bevacizumab 10 mg/kg intravenously every 2 weeks (arm A) or the same plus TRC105 10 mg/kg intravenously every 2 weeks (arm B). The primary endpoint was progression-free survival (PFS) at 12 and 24 weeks. Correlative studies included serum transforming growth factor β (TGFβ) and CD105 levels as well as tissue immunostaining for TGFβ receptors.Fifty-nine patients were enrolled (28 on arm A and 31 on arm B), and 1 patient on each arm had a confirmed partial response. The median PFS for bevacizumab alone was 4.6 months compared with 2.8 for bevacizumab plus TRC105 (P = .09). Grade ≥ 3 toxicities occurred in 16 patients (57%) who received bevacizumab compared with 19 (61%) who received bevacizumab plus TRC105 (P = .9). Baseline serum TGFβ levels below the median (<10.6 ng/mL) were associated with longer median PFS (5.6 vs 2.1 months; P = .014).TRC105 failed to improve PFS when added to bevacizumab. TGFβ warrants further study as a biomarker in RCC. Cancer 2017;123:4566-4573. © 2017 American Cancer Society. |
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