Vorinostat Downregulates the Expression of CD30 and Lowers the Efficacy of Brentuximab Vedotin

Over the last decade, the number of clinical trials looking at combination therapies has been been growing. As a result, the potential of drug-drug interactions require real attention. One trial included the treatment of CD30+ tumors after previous vorinostat (Zolinza®; Merck, Sharp & Dohme/Merck & Co, Inc, also known as suberanilohydroxamic acid (suberoyl+anilide+hydroxamic acid abbreviated as SAHA) failure with the anti-CD30 antibody-drug conjugate brentuximab vedotin (Adcetris®; Seattle Genetics)‎

Using B-, T- and NK-cell lines in vitro, Professor Clare Sample, PhD, at the Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, in Hershey, PA, and her team, demonstrated that SAHA downregulates the expression of CD30 and lowers the efficacy of subsequent brentuximab vedotin treatment if baseline CD30 levels are reduced by 50% or more.

The researchers noted that low dose SAHA treatment that maintained 50% or more of basal CD30 expression followed by subsequent treatment with brentuximab vedotin led to enhanced anti-tumor activity. However, the downregulation of CD30 was short lived upon SAHA removal. This suggest that allowing SAHA washout may circumvent any interactions with subsequent drug therapies.

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In their article published in the October 15, 2014 online first edition of Molecular Cancer Therapeutics, Sample and her collegues write that their findings confirm the requirement of CD30 for brentuximab vedotin efficacy and suggest that combination treatment with SAHA in CD30dim tumors may decrease efficacy. They conclude Cthat combination treatment in highly CD30+ tumors, however, increases efficacy and warrants further consideration as a new treatment paradigm.

Published in: Molecular Cancer Therapeutics