A Randomized Phase II Study to Determine the Effect of 2 Different Doses of Aflibercept in Patients With Metastatic Renal Cell Carcinoma (ECOG-ACRIN [E4805])

Roberto Pili, Opeyemi Jegede, Michael A. Carducci, Judith Manola, David L. Groteluschen, Leonard L. Appleman, Glenn Liu, James C. Shanks, Shaker R. Dakhil, Janice Dutcher, Robert S. DiPaola

Research output: Contribution to journalArticle

Abstract

Background: Aflibercept is a recombinantly produced fusion protein that has potent anti-vascular endothelial growth factor (VEGF) activity. We tested whether aflibercept has clinical activity in clear-cell renal cell carcinoma (ccRCC). The recommended phase II dose was 4 mg/kg but several patients (pts) treated at 1 mg/kg showed prolonged progression-free survival. We therefore tested both doses in a parallel group randomized trial. Patients and Methods: Eligible pts had histologically confirmed advanced or metastatic ccRCC and previous treatments included exposure to a VEGF receptor tyrosine kinase inhibitor. Pts received aflibercept (either 1 mg/kg or 4 mg/kg) on day 1 of a 14-day cycle until disease progression. Pts randomized to 1 mg/kg could crossover to 4 mg/kg at the time of disease progression. The primary end point was proportion alive and progression-free at 8 weeks. A Simon 2-stage design was used for each arm with 33 and 24 eligible pts per arm enrolled in stages 1 and 2. Results: Ninety-four pts were enrolled, 59 and 35 to 4 mg and 1 mg doses, respectively. Seventy-two percent had 1 previous treatment most commonly sunitinib. Sixteen eligible pts crossed over at the time of disease progression to the 4-mg dose. Most common adverse events were hypertension, proteinuria, and fatigue. Only 4 pts reported Grade 4 or higher toxicity. With 36 of 59 pts (61%) progression-free at 8 weeks, the 4-mg/kg dose met protocol-specified efficacy criteria. Conclusion: Aflibercept is active in previously treated ccRCC and might be worthy of further study.

Original languageEnglish (US)
JournalClinical Genitourinary Cancer
DOIs
StateAccepted/In press - Jan 5 2017
Externally publishedYes

Fingerprint

Renal Cell Carcinoma
Disease Progression
Vascular Endothelial Growth Factor Receptor
aflibercept
Proteinuria
Protein-Tyrosine Kinases
Vascular Endothelial Growth Factor A
Disease-Free Survival
Fatigue
Hypertension
Therapeutics
Proteins

Keywords

  • Angiogenesis inhibitor
  • Antiangiogenesis
  • Drug resistance
  • VEGF blocker

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

A Randomized Phase II Study to Determine the Effect of 2 Different Doses of Aflibercept in Patients With Metastatic Renal Cell Carcinoma (ECOG-ACRIN [E4805]). / Pili, Roberto; Jegede, Opeyemi; Carducci, Michael A.; Manola, Judith; Groteluschen, David L.; Appleman, Leonard L.; Liu, Glenn; Shanks, James C.; Dakhil, Shaker R.; Dutcher, Janice; DiPaola, Robert S.

In: Clinical Genitourinary Cancer, 05.01.2017.

Research output: Contribution to journalArticle

Pili, Roberto ; Jegede, Opeyemi ; Carducci, Michael A. ; Manola, Judith ; Groteluschen, David L. ; Appleman, Leonard L. ; Liu, Glenn ; Shanks, James C. ; Dakhil, Shaker R. ; Dutcher, Janice ; DiPaola, Robert S. / A Randomized Phase II Study to Determine the Effect of 2 Different Doses of Aflibercept in Patients With Metastatic Renal Cell Carcinoma (ECOG-ACRIN [E4805]). In: Clinical Genitourinary Cancer. 2017.
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abstract = "Background: Aflibercept is a recombinantly produced fusion protein that has potent anti-vascular endothelial growth factor (VEGF) activity. We tested whether aflibercept has clinical activity in clear-cell renal cell carcinoma (ccRCC). The recommended phase II dose was 4 mg/kg but several patients (pts) treated at 1 mg/kg showed prolonged progression-free survival. We therefore tested both doses in a parallel group randomized trial. Patients and Methods: Eligible pts had histologically confirmed advanced or metastatic ccRCC and previous treatments included exposure to a VEGF receptor tyrosine kinase inhibitor. Pts received aflibercept (either 1 mg/kg or 4 mg/kg) on day 1 of a 14-day cycle until disease progression. Pts randomized to 1 mg/kg could crossover to 4 mg/kg at the time of disease progression. The primary end point was proportion alive and progression-free at 8 weeks. A Simon 2-stage design was used for each arm with 33 and 24 eligible pts per arm enrolled in stages 1 and 2. Results: Ninety-four pts were enrolled, 59 and 35 to 4 mg and 1 mg doses, respectively. Seventy-two percent had 1 previous treatment most commonly sunitinib. Sixteen eligible pts crossed over at the time of disease progression to the 4-mg dose. Most common adverse events were hypertension, proteinuria, and fatigue. Only 4 pts reported Grade 4 or higher toxicity. With 36 of 59 pts (61{\%}) progression-free at 8 weeks, the 4-mg/kg dose met protocol-specified efficacy criteria. Conclusion: Aflibercept is active in previously treated ccRCC and might be worthy of further study.",
keywords = "Angiogenesis inhibitor, Antiangiogenesis, Drug resistance, VEGF blocker",
author = "Roberto Pili and Opeyemi Jegede and Carducci, {Michael A.} and Judith Manola and Groteluschen, {David L.} and Appleman, {Leonard L.} and Glenn Liu and Shanks, {James C.} and Dakhil, {Shaker R.} and Janice Dutcher and DiPaola, {Robert S.}",
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T1 - A Randomized Phase II Study to Determine the Effect of 2 Different Doses of Aflibercept in Patients With Metastatic Renal Cell Carcinoma (ECOG-ACRIN [E4805])

AU - Pili, Roberto

AU - Jegede, Opeyemi

AU - Carducci, Michael A.

AU - Manola, Judith

AU - Groteluschen, David L.

AU - Appleman, Leonard L.

AU - Liu, Glenn

AU - Shanks, James C.

AU - Dakhil, Shaker R.

AU - Dutcher, Janice

AU - DiPaola, Robert S.

PY - 2017/1/5

Y1 - 2017/1/5

N2 - Background: Aflibercept is a recombinantly produced fusion protein that has potent anti-vascular endothelial growth factor (VEGF) activity. We tested whether aflibercept has clinical activity in clear-cell renal cell carcinoma (ccRCC). The recommended phase II dose was 4 mg/kg but several patients (pts) treated at 1 mg/kg showed prolonged progression-free survival. We therefore tested both doses in a parallel group randomized trial. Patients and Methods: Eligible pts had histologically confirmed advanced or metastatic ccRCC and previous treatments included exposure to a VEGF receptor tyrosine kinase inhibitor. Pts received aflibercept (either 1 mg/kg or 4 mg/kg) on day 1 of a 14-day cycle until disease progression. Pts randomized to 1 mg/kg could crossover to 4 mg/kg at the time of disease progression. The primary end point was proportion alive and progression-free at 8 weeks. A Simon 2-stage design was used for each arm with 33 and 24 eligible pts per arm enrolled in stages 1 and 2. Results: Ninety-four pts were enrolled, 59 and 35 to 4 mg and 1 mg doses, respectively. Seventy-two percent had 1 previous treatment most commonly sunitinib. Sixteen eligible pts crossed over at the time of disease progression to the 4-mg dose. Most common adverse events were hypertension, proteinuria, and fatigue. Only 4 pts reported Grade 4 or higher toxicity. With 36 of 59 pts (61%) progression-free at 8 weeks, the 4-mg/kg dose met protocol-specified efficacy criteria. Conclusion: Aflibercept is active in previously treated ccRCC and might be worthy of further study.

AB - Background: Aflibercept is a recombinantly produced fusion protein that has potent anti-vascular endothelial growth factor (VEGF) activity. We tested whether aflibercept has clinical activity in clear-cell renal cell carcinoma (ccRCC). The recommended phase II dose was 4 mg/kg but several patients (pts) treated at 1 mg/kg showed prolonged progression-free survival. We therefore tested both doses in a parallel group randomized trial. Patients and Methods: Eligible pts had histologically confirmed advanced or metastatic ccRCC and previous treatments included exposure to a VEGF receptor tyrosine kinase inhibitor. Pts received aflibercept (either 1 mg/kg or 4 mg/kg) on day 1 of a 14-day cycle until disease progression. Pts randomized to 1 mg/kg could crossover to 4 mg/kg at the time of disease progression. The primary end point was proportion alive and progression-free at 8 weeks. A Simon 2-stage design was used for each arm with 33 and 24 eligible pts per arm enrolled in stages 1 and 2. Results: Ninety-four pts were enrolled, 59 and 35 to 4 mg and 1 mg doses, respectively. Seventy-two percent had 1 previous treatment most commonly sunitinib. Sixteen eligible pts crossed over at the time of disease progression to the 4-mg dose. Most common adverse events were hypertension, proteinuria, and fatigue. Only 4 pts reported Grade 4 or higher toxicity. With 36 of 59 pts (61%) progression-free at 8 weeks, the 4-mg/kg dose met protocol-specified efficacy criteria. Conclusion: Aflibercept is active in previously treated ccRCC and might be worthy of further study.

KW - Angiogenesis inhibitor

KW - Antiangiogenesis

KW - Drug resistance

KW - VEGF blocker

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