Multicentre phase II trial of cabozantinib in patients with hepatocellular carcinoma after immune checkpoint inhibitor treatment

Abstract

Background and Aims

There has been a lack of prospective data on treatment after immune checkpoint inhibitor (ICI) in hepatocellular carcinoma (HCC). We conducted a phase II multicentred study on cabozantinib in HCC after ICI treatment.

Methods

This is an investigator-initiated single-arm clinical trial involving academic centres in Hong Kong and Korea. Key eligibility criteria include diagnosis of HCC; refractoriness to prior ICI-based treatment; Child-Pugh A liver function. Maximally two prior lines of therapy were allowed. All patients were commenced cabozantinib at 60mg/day. The primary endpoint was progression-free survival (PFS).

Results

Total 47 patients were recruited from Oct 2020 to May 2022. The median follow-up was 11.2 months. In the study, 27 and 20 patients received one and two prior therapies. The median PFS was 4.1 months (95%CI:3.3-5.3). The median 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%) of patients. When used as a second-line treatment (n=20), cabozantinib was associated with a median PFS and OS of 4.3 (95%CI:3.3-6.7) and 14.3 months (95%CI:8.9-NR). The corresponding median PFS and OS was 4.3 (95%CI:3.3-11.0) and 14.3 months (95%CI:9.0-NR) for those receiving ICI-based regimen with proven benefits (n=17). Commonest grade 3-4 TRAE was thrombocytopenia (6.4%). The median dose of cabozantinib was 40mg/day. The number of prior therapy was an independent prognosticator (one vs. two; HR=0.37; p=0.03).

Conclusions

Cabozantinib demonstrates efficacy in patients with prior ICI. The survival data of second-line cabozantinib following the first-line ICI regimen provide reference for clinical trial testing post-ICI therapy. The number of prior line of treatment may be considered a stratification factor in randomized study.

Impact and Implications

There is a lack of prospective data on systemic therapy following prior immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC). The current phase II clinical trial reported the efficacy and safety data of cabozantinib in patients with prior ICI-based treatment. Exploratory analyses showed that the performance of cabozantinib differed significantly when used as second or third-line treatment. The above data could be used a reference for clinical practice and design of future clinical trials on subsequent treatment following ICIs.

Trial registration

ClinicalTrials.gov Identifier: NCT04588051.