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
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Article info
Publication history
Published online: April 25, 2017
Accepted:
April 14,
2017
Received in revised form:
April 11,
2017
Received:
January 5,
2017
Footnotes
ClinicalTrials.gov: NCT00894504.
Current address for Janice Dutcher: Cancer Research Foundation of New York, New York, NY.
Current address for Robert S. DiPaola: University of Kentucky, Lexington, KY.
Identification
Copyright
© 2017 Elsevier Inc. All rights reserved.
