Jordi Bruix, MD, PhD

Flavio G. Rocha, MD

Discussant Jordi Bruix, MD, PhD, Head of the Barcelona Clinic Liver Cancer Group at the University of Barcelona in Spain, said the results of the CELESTIAL trial show that cabozantinib (Cabometyx) provides a clinically meaningful survival benefit to patients with advanced hepatocellular carcinoma who have exhausted sorafenib. However, he expressed concern that treatment appeared to be interrupted in many patients, leading to questions about the drug’s tolerability.

“This is something I would like to see better explored, to understand to what extent the drug is safe and can be managed,” Dr. Bruix said.

Almost all of the systemic therapies that have shown efficacy in advanced disease—sorafenib (Nexavar), lenvatinib (Lenvima), regorafenib (Stivarga), and now cabozantinib—target the vascular endothelial growth factor (VEGF) pathway, Dr. Bruix remarked. “Patients who may not benefit from anti-VEGF agents are still in need of effective treatments, with survival benefit based on phase III trials,” he said.

‘Even Bigger Question’

Session moderator Flavio G. Rocha, MD, of Virginia Mason Hospital and Medical Center, Seattle, commented: “It’s exciting to have tyrosine kinase inhibitors with efficacy” against advanced hepatocellular carcinoma, “but as new drugs come along, the challenge will be where to sequence them.”

The “even bigger question” now, he added, is how tyrosine kinase inhibitors will measure up against immunotherapy, which physicians are increasingly interested in incorporating. “Now that nivolumab [Opdivo] is approved, I see doctors who, after failure on sorafenib, will jump directly to checkpoint inhibitors.” ■

DISCLOSURE: Dr. Bruix is a consultant or advisor for Argyle, Bayer Schering Pharma, Bristol-Myers Squibb, BTG Pharmaceuticals, Eisai, Kowa, Novartis, Onxeo, Roche, and Sirtex Medical; is a member of speakers bureaus for Bayer Schering Pharma, BTG Pharmaceuticals, and Sirtex Medical; and has received research funding from Bayer Schering Pharma. Dr. Rocha reported no conflicts of interest.