EMCC: Veliparib Plus Temozolomide in Metastatic Melanoma Trends Toward Increased PFS but Results Are Not Statistically Significant

Dr. Mark Middleton from the University of Oxford in the UK presented the results that veliparib combined with temozolomide (TMZ) nearly doubled the numerical median progression-free survival (PFS) compared to TMZ alone, but that these differences were not statistically significant.

The study was a three-arm, double-blind, placebo-controlled study comparing the efficacy of 20 mg or 40 mg veliparib + TMZ to placebo + TMZ in prolonging progression-free survival (PFS). The trial included 346 stage III or IV metastatic melanoma patients who were randomized 1:1:1. More than 90% of patients in the trial had stage IV melanoma, with approximately 10% having had a history of brain metastases.

"Both veliparib arms outperformed the control group, but with no statistical impact on survival," said Dr. Middleton. Dr. J. Hansson from the Karolinska Institute in Stockholm, Sweden, the discussant for the study presentation, suggested that the trial may not have been "powered to have the hazard ratio translate into a statistically significant signal." 

The median PFS for the 20-mg veliparib group was 113 days (P = .071) and 110 days for the 40-mg veliparib group (P = .24), compared with 60 days in the TMZ-alone treatment group. Overall survival was not impacted by the addition of veliparib to the TMZ regimen. Toxicities were in line with those seen with TMZ monotherapy treatment and included gastrointestinal and hematological events. Grade 3 and 4 toxicities were higher in the veliparib 20-mg and 40-mg treatment arms compared to the control arm (54.3%, 56.5%, and 38.1%, respectively).

Dr. Middleton concluded that the combination treatment was well tolerated. Biomarker studies are ongoing to identify potential subpopulations that could benefit from this treatment regimen, as the data suggest that there may be promising results with some patients based on the PFS data.

Veliparib (ABT-888) is a novel, oral, small molecule PARP inhibitor. Preclinical data show that veliparib enhances the anti-tumor activity of several cytotoxic agents including TMZ. It is currently used in liver, ovarian, and metastatic breast cancers in combination with TMZ.