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Phase III COSMIC-312 Trial: Cabozantinib Plus Atezolizumab Versus Sorafenib in Advanced Liver Cancer

By: Kayci Reyer
Posted: Friday, September 30, 2022

According to findings from the phase III COSMIC-312 trial presented in The Lancet Oncology, some patients with advanced hepatocellular carcinoma may benefit from a combination treatment of the tyrosine kinase inhibitor cabozantinib plus the monoclonal antibody atezolizumab. Although the dual therapy did not improve overall survival, it was associated with positive impacts on progression-free survival and disease control.

“For some patients, delaying progression and achieving rapid disease control is particularly important, such as in symptomatic patients with high disease burden or main portal vein occlusion at risk for impending complications,” noted Robin Kate Kelley, MD, of the University of California San Francisco Helen Diller Family Comprehensive Cancer Center, and colleagues. “The observed improvement in progression-free survival in subgroups with more advanced malignancy, including those with extrahepatic disease or macrovascular invasion, reinforces the assessment of clinical benefit.”

From December 2018 through August 2020, a total of 837 patients were randomly assigned to receive either cabozantinib plus atezolizumab (n = 432), sorafenib monotherapy (n = 217), or cabozantinib monotherapy (n = 188). Eligible patients, located across 32 countries, had advanced disease that was not receptive to curative or locoregional treatments and who were systemic anticancer treatment-naive.

Median overall survival was comparable with the combination treatment and sorafenib (15.4 months vs. 15.5 months). However, the group that received the doublet experienced superior median progression-free survival versus the group given sorafenib (6.8 months vs. 4.2 months). In the combination, sorafenib, and cabozantinib groups, aminotransferase increase (9% vs. 3% vs. 6%), hypertension (9% vs. 8% vs. 12%), aspartate aminotransferase increase (9% vs. 4% vs. 10%), and palmar-plantar erythrodysesthesia (8% vs. 8% vs. 9%) were the most commonly reported grade 3 or 4 adverse events.

Disclosure: For full disclosures of the study authors, visit

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