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Randomized Controlled Trial
. 2017 Dec 1;123(23):4566-4573.
doi: 10.1002/cncr.30942. Epub 2017 Aug 22.

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

Tanya B Dorff  1 , Jeff A Longmate  2 , Sumanta K Pal  3 , Walter M Stadler  4 , Mayer N Fishman  5 , Ulka N Vaishampayan  6 , Amol Rao  1 , Jacek K Pinksi  1 , James S Hu  1 , David I Quinn  7 , Primo N Lara Jr  8
Affiliations
Randomized Controlled Trial

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

Tanya B Dorff et al. Cancer. .

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.

Keywords: angiogenesis; renal cancer; targeted therapy; transforming growth factor β (TGFβ); vascular endothelial growth factor (VEGF).

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Conflict of interest statement

Conflict of interest disclosure:

TBD: consultant for Bayer, Genentech, Pfizer. Speaker for Astellas, Dendreon, Exelixis. JL: none. SKP: WS: MF: consultant to Bayer, Alkermes, Medivation; speaker for Dendreon. UV: AR: JP: consultant for Aeterna-Zentaris, Astellas, Bayer, Dendreon, Janssen, Millenium

Figures

Figure 1
Figure 1
CONSORT diagram depicting subject accrual, randomization
Figure 2
Figure 2
Kaplan-Meier Curves depicting (A) overall survival and (B) time to treatment failure for the study arms.
Figure 2
Figure 2
Kaplan-Meier Curves depicting (A) overall survival and (B) time to treatment failure for the study arms.
See this image and copyright information in PMC

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