Abstract
Background—Aflibercept is a recombinantly-produced fusion protein that has potent anti-VEGF activity. We tested whether aflibercept has clinical activity in clear cell renal cell carcinoma (ccRCC). The recommended Phase 2 dose was 4 mg/kg but several patients treated at 1 mg/kg demonstrated prolonged progression-free survival (PFS). We therefore tested both doses in a parallel group randomized trial.
Methods—Eligible patients (pts) had histologically confirmed advanced or metastatic ccRCC and previous treatments including prior exposure to a VEGF RTKI. Patients received aflibercept (either 1 mg/kg or 4 mg/kg) day 1 of a 14-day cycle until progression. Patients randomized to 1 mg/kg could crossover to 4 mg/kg at progression. The primary endpoint 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/arm enrolled in stages 1 and 2.
Results—94 pts were enrolled, 59 and 35 to 4 mg and 1 mg doses, respectively. 72% had 1 prior tx most commonly sunitinib. 16 eligible pts crossed over at 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 36/59 (61%) pts PFS at 8 wks, the 4-mg/kg dose met protocol specified efficacy criteria.
Conclusions—Aflibercept is active in previously treated ccRCC and may be worthy of further study.
Document Type
Article
Publication Date
12-2017
Digital Object Identifier (DOI)
https://doi.org/10.1016/j.clgc.2017.04.023
Funding Information
This study was conducted by the ECOG-ACRIN Cancer Research Group (Robert L. Comis, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported in part by Public Health Service Grants CA180820, CA180794, CA180802, CA180844, and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services.
Related Content
Refer to Web version on PubMed Central for supplementary material.
Repository Citation
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; and DiPaola, Robert S., "ECOG-ACRIN (E4805) Randomized Phase II Study to Determine the Effect of 2 Different Doses of Aflibercept in Patients with Metastatic Renal Cell Carcinoma" (2017). Internal Medicine Faculty Publications. 177.
https://uknowledge.uky.edu/internalmedicine_facpub/177
Supplemental Figure 1.
Notes/Citation Information
Published in Clinical Genitourinary Cancer, v. 15, issue 6, p. 642-651.e1.
© 2017 Elsevier Inc. All rights reserved.
This manuscript version is made available under the CC‐BY‐NC‐ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/.
The document available for download is the author's post-peer-review final draft of the article.