Phase II study of aflibercept (VEGF-Trap) in patients with recurrent or metastatic urothelial cancer, a california cancer consortium trial

Przemyslaw Twardowski, Walter M. Stadler, Paul Frankel, Primo N Lara, Christopher Ruel, Gurkamal Chatta, Elisabeth Heath, David I. Quinn, David R Gandara

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

OBJECTIVES: To determine whether aflibercept, a recombinant fusion protein that binds and neutralizes multiple vascular endothelial growth factor isoforms, is effective in the treatment of urothelial cancer. The efficacy of systemic therapies for advanced urothelial cancer after failure of front-line platinum-based chemotherapy is limited. Evidence has shown that vascular endothelial growth factor is important in the pathophysiology of urothelial cancer. METHODS: Patients with measurable, metastatic, or locally advanced urothelial cancer previously treated with 1 platinum-containing regimen were enrolled. Aflibercept was administered at 4 mg/kg intravenously every 2 weeks. The response rate (RR) and progression-free survival (PFS) were assessed in a 2-stage accrual design (22 + 18). A maximum of 40 patients were to be accrued to rule out a null hypothesis RR of 4% and PFS of 3 months versus an alternative RR of 15% and PFS of 5.4 months, with α = 0.12 and β = 0.19. RESULTS: A total of 22 patients were accrued. One partial response (4.5% RR, 95% confidence interval 0.1%-22.8%) was seen. The median PFS was 2.79 months (95% confidence interval 1.74-3.88). Attributable Grade 3 toxicities included fatigue, hypertension, proteinuria, pulmonary hemorrhage, pain, hyponatremia, anorexia, and lymphopenia. No treatment-related Grade 4 or greater toxicities occurred. CONCLUSIONS: Aflibercept was well tolerated, with toxicity similar to those seen with other vascular endothelial growth factor pathway inhibitors; however, it had limited single-agent activity in patients with urothelial carcinoma previously treated with platinum-containing chemotherapy.

Original languageEnglish (US)
Pages (from-to)923-926
Number of pages4
JournalUrology
Volume76
Issue number4
DOIs
StatePublished - Oct 2010

Fingerprint

Disease-Free Survival
Platinum
Vascular Endothelial Growth Factor A
Neoplasms
Confidence Intervals
Recombinant Fusion Proteins
Drug Therapy
Lymphopenia
Hyponatremia
Anorexia
Proteinuria
Pulmonary Hypertension
Fatigue
Protein Isoforms
Therapeutics
Hemorrhage
Carcinoma
Pain
aflibercept

ASJC Scopus subject areas

  • Urology

Cite this

Phase II study of aflibercept (VEGF-Trap) in patients with recurrent or metastatic urothelial cancer, a california cancer consortium trial. / Twardowski, Przemyslaw; Stadler, Walter M.; Frankel, Paul; Lara, Primo N; Ruel, Christopher; Chatta, Gurkamal; Heath, Elisabeth; Quinn, David I.; Gandara, David R.

In: Urology, Vol. 76, No. 4, 10.2010, p. 923-926.

Research output: Contribution to journalArticle

Twardowski, Przemyslaw ; Stadler, Walter M. ; Frankel, Paul ; Lara, Primo N ; Ruel, Christopher ; Chatta, Gurkamal ; Heath, Elisabeth ; Quinn, David I. ; Gandara, David R. / Phase II study of aflibercept (VEGF-Trap) in patients with recurrent or metastatic urothelial cancer, a california cancer consortium trial. In: Urology. 2010 ; Vol. 76, No. 4. pp. 923-926.
@article{60fff6f344ce4f0da4722b3d864a96cc,
title = "Phase II study of aflibercept (VEGF-Trap) in patients with recurrent or metastatic urothelial cancer, a california cancer consortium trial",
abstract = "OBJECTIVES: To determine whether aflibercept, a recombinant fusion protein that binds and neutralizes multiple vascular endothelial growth factor isoforms, is effective in the treatment of urothelial cancer. The efficacy of systemic therapies for advanced urothelial cancer after failure of front-line platinum-based chemotherapy is limited. Evidence has shown that vascular endothelial growth factor is important in the pathophysiology of urothelial cancer. METHODS: Patients with measurable, metastatic, or locally advanced urothelial cancer previously treated with 1 platinum-containing regimen were enrolled. Aflibercept was administered at 4 mg/kg intravenously every 2 weeks. The response rate (RR) and progression-free survival (PFS) were assessed in a 2-stage accrual design (22 + 18). A maximum of 40 patients were to be accrued to rule out a null hypothesis RR of 4{\%} and PFS of 3 months versus an alternative RR of 15{\%} and PFS of 5.4 months, with α = 0.12 and β = 0.19. RESULTS: A total of 22 patients were accrued. One partial response (4.5{\%} RR, 95{\%} confidence interval 0.1{\%}-22.8{\%}) was seen. The median PFS was 2.79 months (95{\%} confidence interval 1.74-3.88). Attributable Grade 3 toxicities included fatigue, hypertension, proteinuria, pulmonary hemorrhage, pain, hyponatremia, anorexia, and lymphopenia. No treatment-related Grade 4 or greater toxicities occurred. CONCLUSIONS: Aflibercept was well tolerated, with toxicity similar to those seen with other vascular endothelial growth factor pathway inhibitors; however, it had limited single-agent activity in patients with urothelial carcinoma previously treated with platinum-containing chemotherapy.",
author = "Przemyslaw Twardowski and Stadler, {Walter M.} and Paul Frankel and Lara, {Primo N} and Christopher Ruel and Gurkamal Chatta and Elisabeth Heath and Quinn, {David I.} and Gandara, {David R}",
year = "2010",
month = "10",
doi = "10.1016/j.urology.2010.04.025",
language = "English (US)",
volume = "76",
pages = "923--926",
journal = "Urology",
issn = "1527-9995",
publisher = "Elsevier Inc.",
number = "4",

}

TY - JOUR

T1 - Phase II study of aflibercept (VEGF-Trap) in patients with recurrent or metastatic urothelial cancer, a california cancer consortium trial

AU - Twardowski, Przemyslaw

AU - Stadler, Walter M.

AU - Frankel, Paul

AU - Lara, Primo N

AU - Ruel, Christopher

AU - Chatta, Gurkamal

AU - Heath, Elisabeth

AU - Quinn, David I.

AU - Gandara, David R

PY - 2010/10

Y1 - 2010/10

N2 - OBJECTIVES: To determine whether aflibercept, a recombinant fusion protein that binds and neutralizes multiple vascular endothelial growth factor isoforms, is effective in the treatment of urothelial cancer. The efficacy of systemic therapies for advanced urothelial cancer after failure of front-line platinum-based chemotherapy is limited. Evidence has shown that vascular endothelial growth factor is important in the pathophysiology of urothelial cancer. METHODS: Patients with measurable, metastatic, or locally advanced urothelial cancer previously treated with 1 platinum-containing regimen were enrolled. Aflibercept was administered at 4 mg/kg intravenously every 2 weeks. The response rate (RR) and progression-free survival (PFS) were assessed in a 2-stage accrual design (22 + 18). A maximum of 40 patients were to be accrued to rule out a null hypothesis RR of 4% and PFS of 3 months versus an alternative RR of 15% and PFS of 5.4 months, with α = 0.12 and β = 0.19. RESULTS: A total of 22 patients were accrued. One partial response (4.5% RR, 95% confidence interval 0.1%-22.8%) was seen. The median PFS was 2.79 months (95% confidence interval 1.74-3.88). Attributable Grade 3 toxicities included fatigue, hypertension, proteinuria, pulmonary hemorrhage, pain, hyponatremia, anorexia, and lymphopenia. No treatment-related Grade 4 or greater toxicities occurred. CONCLUSIONS: Aflibercept was well tolerated, with toxicity similar to those seen with other vascular endothelial growth factor pathway inhibitors; however, it had limited single-agent activity in patients with urothelial carcinoma previously treated with platinum-containing chemotherapy.

AB - OBJECTIVES: To determine whether aflibercept, a recombinant fusion protein that binds and neutralizes multiple vascular endothelial growth factor isoforms, is effective in the treatment of urothelial cancer. The efficacy of systemic therapies for advanced urothelial cancer after failure of front-line platinum-based chemotherapy is limited. Evidence has shown that vascular endothelial growth factor is important in the pathophysiology of urothelial cancer. METHODS: Patients with measurable, metastatic, or locally advanced urothelial cancer previously treated with 1 platinum-containing regimen were enrolled. Aflibercept was administered at 4 mg/kg intravenously every 2 weeks. The response rate (RR) and progression-free survival (PFS) were assessed in a 2-stage accrual design (22 + 18). A maximum of 40 patients were to be accrued to rule out a null hypothesis RR of 4% and PFS of 3 months versus an alternative RR of 15% and PFS of 5.4 months, with α = 0.12 and β = 0.19. RESULTS: A total of 22 patients were accrued. One partial response (4.5% RR, 95% confidence interval 0.1%-22.8%) was seen. The median PFS was 2.79 months (95% confidence interval 1.74-3.88). Attributable Grade 3 toxicities included fatigue, hypertension, proteinuria, pulmonary hemorrhage, pain, hyponatremia, anorexia, and lymphopenia. No treatment-related Grade 4 or greater toxicities occurred. CONCLUSIONS: Aflibercept was well tolerated, with toxicity similar to those seen with other vascular endothelial growth factor pathway inhibitors; however, it had limited single-agent activity in patients with urothelial carcinoma previously treated with platinum-containing chemotherapy.

UR - http://www.scopus.com/inward/record.url?scp=77957756488&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77957756488&partnerID=8YFLogxK

U2 - 10.1016/j.urology.2010.04.025

DO - 10.1016/j.urology.2010.04.025

M3 - Article

C2 - 20646741

AN - SCOPUS:77957756488

VL - 76

SP - 923

EP - 926

JO - Urology

JF - Urology

SN - 1527-9995

IS - 4

ER -