Cabozantinib plus atezolizumab versus sorafenib for advanced hepatocellular carcinoma (COSMIC-312): a multicentre, open-label, randomised, phase 3 trial
This is the report of a randomized phase 3 trial assessing the efficacy and safety of first-line cabozantinib plus atezolizumab versus sorafenib in patients with unresectable HCC. 837 patients were randomized 2:1:1 to receive cabozantinib 40 mg orally once daily plus atezolizumab 1200 mg i.v. every 3 weeks (N=432), sorafenib 400 mg orally twice daily (N=217) or single-agent cabozantinib 60 mg orally once daily (=188). Dual primary endpoints were progression-free survival (PFS) per RECIST 1.1 assessed by a blinded independent radiology committee (BIRC) in the first 372 patients assigned to the combination, and overall survival (OS) in all patients assigned to cabozantinib plus atezolizumab or sorafenib. Median PFS (final analysis) was 6.8 months (99%CI 5.6–8.3) in the combination group versus 4.2 months (2.8–7.0) in the sorafenib group (HR 0.63, 99%CI 0.44–0.91, p=0·0012). Median OS (interim analysis) was 15.4 months (96% CI 13.7–17.7) in the combination treatment group versus 15.5 months (12.1–not estimable) in the sorafenib group (HR 0.90, 96% CI 0.69–1.18, p=0.44). The secondary endpoint was PFS per RECIST 1.1 assessed by BIRC for single-agent cabozantinib versus sorafenib. Additional predefined endpoints included objective response rate, duration of response, time to progression, and safety. The most common grade 3-4 adverse events (AEs) were ALT increase (9% in the combination group vs 3% in the sorafenib group vs 6% in the single-agent cabozantinib group), hypertension (9% vs 8% vs 12%), AST increase (9% vs 4% vs 10%), and palmar-plantar erythrodysesthesia (8% vs 8% vs 9%); serious treatment-related AEs occurred in 18% patients in the combination treatment group, 8% patients in the sorafenib group, and 13% in the single-agent cabozantinib group.
The technical storage or access is strictly necessary for the legitimate purpose of enabling the use of a specific service explicitly requested by the subscriber or user, or for the sole purpose of carrying out the transmission of a communication over an electronic communications network.
The technical storage or access is necessary for the legitimate purpose of storing preferences that are not requested by the subscriber or user.
The technical storage or access that is used exclusively for statistical purposes.The technical storage or access that is used exclusively for anonymous statistical purposes. Without a subpoena, voluntary compliance on the part of your Internet Service Provider, or additional records from a third party, information stored or retrieved for this purpose alone cannot usually be used to identify you.
The technical storage or access is required to create user profiles to send advertising, or to track the user on a website or across several websites for similar marketing purposes.