Phase II Trial Shows Overall Survival Benefit With VT-122 Plus Sorafenib in Advanced Hepatocellular Carcinoma


Key Points

  • Patients receiving VT-122 plus sorafenib experienced an overall survival benefit of 11 months compared to those receiving sorafenib alone.
  • The addition of VT-122 to sorafenib was associated with a stabilization of weight loss and reduced incidence of hand-foot syndrome.

The investigational agent VT-122 appeared to benefit survival when combined with sorafenib (Nexavar) in patients with advanced hepatocellular carcinoma, according to data presented at the 8th Annual International Liver Cancer Association Conference in Kyoto, Japan. Researchers reported an 11-month increase in median overall survival in patients treated with VT-122 plus sorafenib, compared to those receiving sorafenib alone.

VT-122 is a novel, oral, chronodosed combination of the nonsteroidal anti-inflammatory drug (NSAID) etodolac and the beta-blocker propranolol. The investigational compound inhibits prostaglandin and beta-adrenergic signaling to reduce tumor-promoting inflammation and restore a tumor-suppressing immune state.

Study Details

In this phase II randomized, open-label, controlled clinical trial, 24 patients with advanced hepatocellular carcinoma were randomly assigned to receive VT-122 plus sorafenib or sorafenib alone.

Patients in the VT-122 plus sorafenib arm had a median overall survival of 21 months compared to 10 months in the sorafenib-alone arm (hazard ratio [HR] = 0.14, P < .001). Of the 12 patients receiving VT-122 plus sorafenib, 10 (83.3%) were alive at 12 months, compared to 3 of 12 patients (25%) in the sorafenib-only group (hazard ratio [HR] = 0.14, P = .004). VT-122 was well tolerated in the study, with no unexpected serious adverse events reported.

The addition of VT-122 to sorafenib was also associated with stabilization of weight loss and reduced incidence of hand-foot syndrome, a major dose-limiting side effect of sorafenib therapy. At 6 months, 42% of patients in the combination therapy arm had gained more than 5% of total body weight, and none had lost more than 5% of body weight. In contrast, 50% of patients receiving sorafenib alone had lost more than 5% of their body weight at 6 months, and none had gained more than 5% of their body weight (P < .05). In addition, only 17% of patients treated with VT-122 plus sorafenib experienced grade 2 hand-foot syndrome, compared to 67% receiving sorafenib alone (P < .05).

“Results of this proof-of-concept trial provide the first evidence that VT-122 is active in hepatocellular carcinoma and suggest a demonstrable survival benefit in patients with advanced disease who are receiving the standard-of-care therapy, sorafenib,” said principal investigator G.S. Bhattacharyya, MD, Head of the Department of Medical Oncology at Fortis Hospitals in Kolkata, India. “Coupled with the growing body of evidence suggesting that the use of NSAIDs and beta-blockers are associated with significant improvement in overall survival in patients with cancer, these results provide a strong basis for advancing VT-122 into further studies for this difficult-to-treat population.”

The study is sponsored by Vicus Therapeutics.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.