LBA1 - A phase II clinical trial to study the efficacy of cabozantinib in patients with hepatocellular carcinoma refractory to immune checkpoint inhibitor-based treatment

Background

There has been a lack of prospective clinical trial data on subsequent treatment after immune checkpoint inhibitor (ICI)-based treatment in HCC. To address this question, we conducted a phase II multicentred study to evaluate the use of cabo in HCC after prior ICI-based treatment.

Methods

This is an investigator-initiated clinical trial involving 3 centres in Hong Kong and Korea. Key eligibility criteria include confirmed diagnosis of HCC; refractoriness to ICI-based treatment; duration of prior ICI-based treatment≥2m; Child's A liver function; maximal 2 lines of therapy. All patients (pts) were started cabo at 60mg once daily till progressive disease or intolerable toxicity. The primary endpoint is progression-free survival (PFS). Other secondary endpoints include response rate (RR) according to the RECIST, overall survival (OS) and treatment-related adverse event (TRAE). Total sample size is 48 (one-sided alpha 0.05; power 80%).

Results

Total 48 pts were recruited from Oct 2020 to May 2022. Data were frozen on 1 Aug 2022 for analyses. The median follow-up was 11.2m. Seven (14.9%) pts remined on treatment; 1pt was excluded from the analysis due to ineligibility. The median age is 61 (Range 36-83). Aetiology of HCC: HBV 34 (72.3%); HCV 2 (4.3%); alcoholic 8 (17%); Most pts have BCLC stage C (93.6%). Total 19 (40.4%) pts have prior atezo-bev (AB) treatment. The median PFS is 4.1m (95% CI 3.3-5.3). About the RR, PR and SD occurs in 3 (6.4%) and 36 (76.6%) pts, respectively. The median OS is 9.9m (95% CI 7.3-14.4) and the 1-year survival rate is 45.3%. Amongst the 19pts with prior AB treatment, the median OS is 14.3m (95% CI: 5.5-14.4) with 1-year survival rate of 50.7%. For prior non-AB regimen, the median OS is 8.9m (95% CI 6.1-NR) with 1-year survival rate of 42.0%. Commonest G3-4 TRAE is thrombocytopenia (6%); hypertension (4%) and ALT elevation (4%). The median dose of cabo is 41.6mg/day (range: 24.3-60.0).

Conclusions

Post-ICI use of cabo is associated with a median PFS of 4.1m and median OS of 9.9m. AB-cabo sequence appears to have more favourable outcome than non-AB-cabo sequence. No new safety signals were observed. This clinical trial reports the first prospective post-ICI survival data on TKI.

Clinical trial identification

NCT04588051.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Ipsen.

Disclosure

S.L. Chan: Financial Interests, Personal, Invited Speaker: AstraZeneca, Eisai, MSD, Bayer, Roche; Financial Interests, Personal, Research Grant: MSD, Bayer, Eisai, Ipsen, SIRTEX. C. Yoo: Financial Interests, Personal, Invited Speaker: Servier, Bayer, AstraZeneca, Merck Sharp & Dohme, Eisai, Celgene, Bristol Myers Squibb, Debiopharm, Ipsen, Kyowa Kirin, Novartis, Boryung Pharmaceuticals, Merck Serono, Mundipharma, Roche, Janssen; Financial Interests, Personal, Research Grant: Servier, Bayer, AstraZeneca, Ono Pharmaceuticals, Celgene, Ipsen, Boryung Pharmaceuticals, Ildong Pharmaceuticals, Chong Kun Dang Pharm, HK. inno.N. All other authors have declared no conflicts of interest.