Bevacizumab alone or in combination with TRC105 for patients with refractory metastatic renal cell cancer. Issue 23 (22nd August 2017)

• Record Type: Journal Article
• Authors: Dorff, Tanya B.; Longmate, Jeff A.; Pal, Sumanta K.; Stadler, Walter M.; Fishman, Mayer N.; Vaishampayan, Ulka N.; Rao, Amol; Pinksi, Jacek K.; Hu, James S.; Quinn, David I.; Lara, Primo N.
• Is Part Of: Cancer. Volume 123:Issue 23(2017)
• Page Start: 4566
• Page End: 4573
• Publication Date: 2017-08-22
• Subjects: angiogenesis -- renal cancer -- targeted therapy -- transforming growth factor β (TGFβ) -- vascular endothelial growth factor (VEGF); Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.30942
• Languages: English
• ISSNs: 0008-543X

Abstract

Abstract : BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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 . Abstract : Adding TRC105 (antiendoglin antibody) to bevacizumab does not prolong progression‐free survival in patients with metastatic renal cell cancer. Serum transforming growth factor β is a biomarker worthy of further study in such patients who receive vascular endothelial growth factor‐targeted therapy.