Cabozantinib + Tecentriq Effective for Liver Cancer?

On July 4, 2022, R.K. Kelley and colleagues from the UCSF Helen Diller Family Comprehensive Cancer Center published the results of the COSMIC-312 Phase III clinical trial in the medical journal "The Lancet Oncology." The study evaluated the effectiveness and safety of Cabozantinib + Tecentriq as a first-line treatment for patients with advanced hepatocellular carcinoma (HCC).

COSMIC-312 was an open-label, multicenter Phase III trial that randomized 837 patients with advanced HCC in a 2:1:1 ratio into three groups: Cabozantinib (40mg once daily) + Tecentriq (1200mg every three weeks) (N=432), sorafenib (400mg twice daily) (N=217), and Cabozantinib monotherapy (60mg once daily) (N=188). The primary endpoints were progression-free survival (PFS) and overall survival (OS).

With a median follow-up of 15.8 months, the median progression-free survival was 6.8 months for the Cabozantinib + Tecentriq group versus 4.2 months for the sorafenib group. The median overall survival was 15.4 months for the Cabozantinib + Tecentriq group compared to 15.5 months for the sorafenib group.

Regarding safety, the incidence of Grade 3-4 side effects included: elevated ALT (Cabozantinib + Tecentriq 9%; sorafenib 3%; Cabozantinib 6%), hypertension (Cabozantinib + Tecentriq 9%; sorafenib 8%; Cabozantinib 12%), elevated AST (Cabozantinib + Tecentriq 9%; sorafenib 4%; Cabozantinib 10%), and hand-foot syndrome (Cabozantinib + Tecentriq 8%; sorafenib 8%; Cabozantinib 9%).

The incidence of serious side effects was 18% in the Cabozantinib + Tecentriq group, 8% in the sorafenib group, and 13% in the Cabozantinib group. Grade 5 adverse events occurred in 1% of patients in the combination group and in less than 1% of patients in both the sorafenib and Cabozantinib monotherapy groups.

Based on the results of the COSMIC-312 trial, R.K. Kelley and others stated that Cabozantinib + Tecentriq as a first-line treatment shows promise as a new therapeutic option for patients with advanced HCC, although additional trials are needed.

Sources: https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(22)00326-6/fulltext

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