Chinese clinical trials of cabozantinib

Background and Purpose: Prospective data following immune checkpoint inhibitor therapy in hepatocellular carcinoma (HCC) are lacking. A phase II multicenter study of cabozantinib following ICI therapy was conducted in HCC.

Methods: This was an investigator-initiated, single-arm clinical trial involving academic centers in Hong Kong and South Korea. Key eligibility criteria include diagnosis of HCC, failure to respond to previous ICI therapy, and Child-Pugh classification of liver function. A maximum of two prior treatments are allowed. All patients were started on cabozantinib 60 mg/day. The primary endpoint is progression-free survival (PFS).

Results: A total of 47 patients were recruited; 27 and 20 patients had received one and two prior treatments, respectively. The median follow-up time was 11.2 months. Median PFS was 4.1 months (95% CI, 3.3-5.3). The median overall survival (OS) was 9.9 months (95% CI, 7.3-14.4), and the 1-year OS rate was 45.3%. Partial response and stable disease occurred in 3 (6.4%) and 36 (76.6%) patients, respectively. When used as second-line therapy (n = 27), median PFS and OS with cabozantinib were 4.3 months (95% CI, 3.3-6.7) and 14.3 months (95% CI, 8.9-NR), respectively. For those patients who received an ICI-based regimen and demonstrated benefit (n=17), the corresponding median PFS and OS were 4.3 months (95% CI, 3.3-11.0) and 14.3 months (95% CI, 9.0-NR), respectively. The most common grade 3-4 treatment-related adverse event was thrombocytopenia (6.4%). The median dose of cabozantinib was 40 mg/day. The number of previous treatments was an independent predictor (1 vs 2; hazard ratio=0.37; p=0.03).

Conclusion: Cabozantinib is effective in patients who have previously receivedICI treatment; the survival data of second-line cabozantinib after first-line ICI regimen provides a reference for future clinical trial design. In randomized studies, the number of prior lines of treatment may be considered a stratification factor.

Impact and Significance: Prospective data on systemic therapy after previous immune checkpoint inhibitor therapy for hepatocellular carcinoma (HCC) are lacking. This Phase II clinical trial provides data on the efficacy and safety of cabozantinib in patients who have previously received ICI-based therapy. Exploratory analyzes showed significant differences in the performance of cabozantinib as second- or third-line therapy. The above data can be used as a reference for clinical practice and future clinical trial design of subsequent treatment lines after ICIs.