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.
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.
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.
Aflibercept is active in previously treated ccRCC and might be worthy of further study.
Clinical genitourinary cancer. 2017 Apr 26 [Epub]
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
Johns Hopkins University, Baltimore, MD. Electronic address: ., Dana Farber Cancer Institute, Boston, MA., Johns Hopkins University, Baltimore, MD., St Vincent Hospital Regional Cancer Center, Green Bay, WI., University of Pittsburgh Cancer Institute, Pittsburgh, PA., University of Wisconsin, Madison, WI., Saint John's Hospital-Healtheast, Maplewood, MN., Cancer Center of Kansas, Wichita, KS., The North Division of Montefiore Medical Center, Bronx, NY., Rutgers Cancer Institute of New Jersey, New Brunswick, NJ.