Details

Autor(en) / Beteiligte

• 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.

Titel

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

Ist Teil von

• Cancer, 2017-12, Vol.123 (23), p.4566-4573

Ort / Verlag

United States: Wiley Subscription Services, Inc

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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.