Atezolizumab and cabozantinib

The global, open-label, phase III COSMIC-312 trial (NCT03755791) included 837 patients with unresectable HCC who had not received prior systemic therapy. Patients were randomly assigned in a 2:1:1 ratio to receive either cabozantinib (40 mg PO daily) with atezolizumab (1,200 mg IV every 3 weeks), sorafenib (400 mg PO bid), or cabozantinib (60 mg daily). Eligibility criteria included intact liver function (Child-Pugh class A), and the study excluded patients with gastric or esophageal varices with active bleeding in the 6 months before enrollment.[11]

The global, open-label, phase III COSMIC-312 trial (NCT03755791) included 837 patients with unresectable HCC who had not received prior systemic therapy. Patients were randomly assigned in a 2:1:1 ratio to receive either cabozantinib (40 mg PO daily) with atezolizumab (1,200 mg IV every 3 weeks), sorafenib (400 mg PO bid), or cabozantinib (60 mg daily). Eligibility criteria included intact liver function (Child-Pugh class A), and the study excluded patients with gastric or esophageal varices with active bleeding in the 6 months before enrollment.[11]

The first primary end point explored median progression-free survival (PFS) in the first 372 patients randomly assigned to combination therapy or sorafenib. Among those patients, the median PFS was 6.8 months (99% CI, 5.6–8.3) in the cabozantinib-atezolizumab arm and 4.2 months (95% CI, 2.8–7.0) in the sorafenib arm (HR, 0.63; 99% CI, 0.44–0.91; P = .0012).[11][Level of evidence B1]

The global, open-label, phase III COSMIC-312 trial (NCT03755791) included 837 patients with unresectable HCC who had not received prior systemic therapy. Patients were randomly assigned in a 2:1:1 ratio to receive either cabozantinib (40 mg PO daily) with atezolizumab (1,200 mg IV every 3 weeks), sorafenib (400 mg PO bid), or cabozantinib (60 mg daily). Eligibility criteria included intact liver function (Child-Pugh class A), and the study excluded patients with gastric or esophageal varices with active bleeding in the 6 months before enrollment.[11]

However, at interim analysis, the OS was similar, at 15.4 months (96% CI, 13.7–17.7) for patients in the cabozantinib-atezolizumab combination arm (n = 432) and 15.5 months (12.1–not estimable) for patients in the sorafenib arm (n = 217) (HR, 0.90; 96% CI, 0.69–1.18; P = .44).

The global, open-label, phase III COSMIC-312 trial (NCT03755791) included 837 patients with unresectable HCC who had not received prior systemic therapy. Patients were randomly assigned in a 2:1:1 ratio to receive either cabozantinib (40 mg PO daily) with atezolizumab (1,200 mg IV every 3 weeks), sorafenib (400 mg PO bid), or cabozantinib (60 mg daily). Eligibility criteria included intact liver function (Child-Pugh class A), and the study excluded patients with gastric or esophageal varices with active bleeding in the 6 months before enrollment.[11]

At interim analysis, the PFS was 5.8 months (99% CI, 5.4–8.2) in the cabozantinib arm and 4.3 months (99% CI, 2.9–6.1) in the sorafenib arm (HR, 0.71; 99% CI, 0.51–1.01; P = .011).

The global, open-label, phase III COSMIC-312 trial (NCT03755791) included 837 patients with unresectable HCC who had not received prior systemic therapy. Patients were randomly assigned in a 2:1:1 ratio to receive either cabozantinib (40 mg PO daily) with atezolizumab (1,200 mg IV every 3 weeks), sorafenib (400 mg PO bid), or cabozantinib (60 mg daily). Eligibility criteria included intact liver function (Child-Pugh class A), and the study excluded patients with gastric or esophageal varices with active bleeding in the 6 months before enrollment.[11]

Objective response rates were 11% (8.1%–14.2%) in the cabozantinib-atezolizumab arm, 4% (1.6%–7.1%) in the sorafenib arm, and 6% (3.3%–10.9%) in the cabozantinib arm.

The global, open-label, phase III COSMIC-312 trial (NCT03755791) included 837 patients with unresectable HCC who had not received prior systemic therapy. Patients were randomly assigned in a 2:1:1 ratio to receive either cabozantinib (40 mg PO daily) with atezolizumab (1,200 mg IV every 3 weeks), sorafenib (400 mg PO bid), or cabozantinib (60 mg daily). Eligibility criteria included intact liver function (Child-Pugh class A), and the study excluded patients with gastric or esophageal varices with active bleeding in the 6 months before enrollment.[11]

Grade 3 or higher treatment-related adverse events occurred in 76% of patients in the cabozantinib-atezolizumab arm, 57% of patients in the sorafenib arm, and 76% of patients in the cabozantinib arm.