Phase II Study Shows the Effect of Adenoviral Vascular Endothelial Growth Factor C and Lymph Node Transfer in Lymphedema.

Abstract

Background: Breast cancer-related lymphedema is a common complication lacking medical treatment. Lymfactin is an adenovirus type 5-based gene therapy and prolymphangiogenic growth factor vector that induces vascular endothelial growth factor C expression. The authors' aim was to evaluate the therapeutic effect of Lymfactin with vascularized lymph node transfer (VLNT).

Methods: This phase II, double-blind, placebo-controlled, randomized, multicenter study evaluated the efficacy and safety of Lymfactin in combination with VLNT. The primary endpoints were edema volume, quality of life, and lymphoscintigraphy. All adverse events were recorded. A mixed model of repeated measures analysis of covariance was performed. This study was a continuation of a previous phase I Lymfactin study.

Results: Thirty-nine patients with breast cancer-related lymphedema were recruited between June of 2018 and December of 2019 and randomized to receive either Lymfactin ( n = 20) or placebo ( n = 19). The primary endpoints showed a positive effect of VLNT in both groups compared with the baseline, but without statistical differences between groups at 12 months. In addition, greater improvements were observed in the tissue dielectric constant ratios measuring skin interstitial fluid levels in the Lymfactin group compared with the placebo group ( P = 0.020). No differences in adverse events were detected between the groups.

Conclusions: This study was one of the few studies to objectively show a positive effect of VLNT in a prospective, clinical, multicenter setting. It was also the first-ever randomized prospective clinical study showing a quantitatively positive effect of a medical therapy on the edema of lymphedema but failed to show differences between groups in primary outcome measures.

Clinical question/level of evidence: Therapeutic, II.