Bevacizumab alone or in combination with TRC105 for patients with refractory metastatic renal cell cancer

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. © 2017 American Cancer Society.

Cancer. 2017 Aug 22 [Epub ahead of print]

Tanya B Dorff, Jeff A Longmate, Sumanta K Pal, Walter M Stadler, Mayer N Fishman, Ulka N Vaishampayan, Amol Rao, Jacek K Pinksi, James S Hu, David I Quinn, Primo N Lara

University of Southern California Keck School of Medicine, Norris Comprehensive Cancer Center, Los Angeles, California., Department of Biostatistics, City of Hope, Duarte, California., Department of Medical Oncology and Experimental Therapeutics, City of Hope, Duarte, California., Hematology/Oncology Section, University of Chicago, Chicago, Illinois., Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida., Department of Hematology and Oncology, Karmanos Cancer Center, Detroit, Michigan., Department of Medical Oncology, University of Southern California Keck School of Medicine, Norris Comprehensive Cancer Center, Los Angeles, California., University of California Davis Comprehensive Cancer Center, Sacramento, California.

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