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

• Authors: 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 Jr
• Journal: Cancer (Cancer) Vol. 123 Issue 23 Pg. 4566-4573 (Dec 01 2017) ISSN: 1097-0142 [Electronic] United States
• PMID: 28832978 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: © 2017 American Cancer Society.

Chemical References

• Antibodies, Monoclonal
• Bevacizumab
• carotuximab

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bevacizumab (administration & dosage)
• Carcinoma, Papillary (drug therapy, secondary)
• Carcinoma, Renal Cell (drug therapy, secondary)
• Female
• Follow-Up Studies
• Humans
• Kidney Neoplasms (drug therapy, pathology)
• Male
• Middle Aged
• Neoplasm Staging
• Prognosis
• Survival Rate