Cabozantinib offers survival benefits to ICI-treated HCC patients

A phase II trial of cabozantinib demonstrates the study drug’s efficacy in patients with hepatocellular carcinoma (HCC) previously treated with immune checkpoint inhibitor (ICI) regimens.

Investigators carried out this single-arm, clinical trial in academic centres in Hong Kong and Korea and included patients with HCC diagnosis, refractoriness to prior ICI-based treatment, and Child-Pugh A liver function. Only those with a maximum of two prior lines of therapy were allowed. Eligible patients initiated cabozantinib 60 mg/day. Progression-free survival (PFS) served as the primary endpoint.

Of the 47 eligible patients with HCC recruited from October 2020 to May 2022, 27 had received one and 20 had received two prior therapies.

Over a median follow-up of 11.2 months, patients achieved a median PFS of 4.1 months (95 percent confidence interval [CI], 3.3‒5.3), a median overall survival (OS) of 9.9 months (95 percent CI, 7.3‒14.4), and 1-year OS rate of 45.3 percent. Three patients (6.4 percent) had partial response, while 36 (76.6 percent) had stable disease.

In 27 patients who used cabozantinib as a second-line treatment, median PFS was 4.3 months (95 percent CI, 3.3‒6.7) and median OS was 14.3 months (95 percent CI, 8.9‒not reached [NR]). For those receiving ICI-based regimens with proven benefits (n=17), median PFS was 4.3 months (95 percent CI, 3.3‒11.0) and median OS was 14.3 months (95 percent CI, 9.0‒NR).

Thrombocytopenia (6.4 percent) was the most common grade 3/4 treatment-related adverse event.

Moreover, the median cabozantinib dose received by patients was 40 mg/day. The number of prior therapies received was an independent prognosticator (1 vs 2; hazard ratio, 0.37; p=0.03).

“[S]urvival data for second-line cabozantinib following first-line ICI regimens provide a reference for future clinical trial design,” the investigators said. “The number of prior lines of treatment may be considered a stratification factor in randomized studies.”