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

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

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)4566-4573
Number of pages8
JournalCancer
Volume123
Issue number23
DOIs
StatePublished - Dec 1 2017

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Renal Cell Carcinoma
Transforming Growth Factors
Disease-Free Survival
Vascular Endothelial Growth Factor A
Growth Factor Receptors
Bevacizumab
TRC105
Serum
Biomarkers
Monoclonal Antibodies
Neoplasms

Keywords

  • angiogenesis
  • renal cancer
  • targeted therapy
  • transforming growth factor β (TGFβ)
  • vascular endothelial growth factor (VEGF)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Dorff, T. B., Longmate, J. A., Pal, S. K., Stadler, W. M., Fishman, M. N., Vaishampayan, U. N., ... Lara, P. N. (2017). Bevacizumab alone or in combination with TRC105 for patients with refractory metastatic renal cell cancer. Cancer, 123(23), 4566-4573. https://doi.org/10.1002/cncr.30942

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

In: Cancer, Vol. 123, No. 23, 01.12.2017, p. 4566-4573.

Research output: Contribution to journalArticle

Dorff, TB, Longmate, JA, Pal, SK, Stadler, WM, Fishman, MN, Vaishampayan, UN, Rao, A, Pinksi, JK, Hu, JS, Quinn, DI & Lara, PN 2017, 'Bevacizumab alone or in combination with TRC105 for patients with refractory metastatic renal cell cancer', Cancer, vol. 123, no. 23, pp. 4566-4573. https://doi.org/10.1002/cncr.30942
Dorff TB, Longmate JA, Pal SK, Stadler WM, Fishman MN, Vaishampayan UN et al. Bevacizumab alone or in combination with TRC105 for patients with refractory metastatic renal cell cancer. Cancer. 2017 Dec 1;123(23):4566-4573. https://doi.org/10.1002/cncr.30942
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. / Bevacizumab alone or in combination with TRC105 for patients with refractory metastatic renal cell cancer. In: Cancer. 2017 ; Vol. 123, No. 23. pp. 4566-4573.
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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.",
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T1 - Bevacizumab alone or in combination with TRC105 for patients with refractory metastatic renal cell cancer

AU - Dorff, Tanya B.

AU - Longmate, Jeff A.

AU - Pal, Sumanta K.

AU - Stadler, Walter M.

AU - Fishman, Mayer N.

AU - Vaishampayan, Ulka N.

AU - Rao, Amol

AU - Pinksi, Jacek K.

AU - Hu, James S.

AU - Quinn, David I.

AU - Lara, Primo N

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

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KW - targeted therapy

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