Sang Youn Hwang
Background: Cabozantinib is approved as second line therapy in patients with progression after sorafenib in hepatocellular carcinoma (HCC) patients, however the study about efficacy of cabozantinib as third or fourth line therapy (esp. in the case of progression after nivolumab). We aimed to evaluate the efficacy and safety of cabozantinib as 3rd & 4th line treatment in patients with advanced HCC with progressive disease after TKI and nivolumab.
Methods: Eligible advanced HCC patients with documented radiological evidence of disease progression with previous 1st & 2nd line systemic treatment were recruited in our hospital from Mar 2019 to Aug 2019. All patients initially received cabozantinib 60mg daily as fixed starting dose every 4 weeks for unlimited cycles untile radiologic progression.
Results: Six patients (3rd line Tx in one patient, 4th line Tx in five patients) were enrolled in the study. All five patients previously received three sequential therapies (sorafenib → regorafenib → nivolumab) and only one patient received two sequential therapies (sorafenib → nivolumab). The median level of AFP was 128.6 ng/mL (1.3-20948), that of PIVKA was 2131 mAU/Ml (1057-29440) in 2L group. The median OS was 5 months (range 3-6.5) and the median PFS was 4 months (range 3-6.5). The OS and in sorafenib responder & non responder were not different significantly (median OS 4 vs 3 months; p-value=0.503). All patient achieved stable disease. Grade 3 or 4 adverse events occurred in 3 patients (66.6%). The most common high-grade events fatigue (50%) and diarrhea (16%). Interruption of drug was happened in all patients within 8 weeks and dose reduction was occurred in 4 patients (66.6%).
Conclusions: Our study suggests that cabozantinib can be relatively effective and safe strategy as 3rd and 4th line therapy in HCC patients refractory for previous systemic therapy. A further well controlled, large scaled study to prove survival benefit is recommended.
Sang Youn Hwang is currently affiliated to the Department of Internal Medicine and Gastrointestinal Cancer Centre in Dongnam Institute of Radiological & Medical Sciences, Republic of Korea
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