Higher risk of hepatotoxicity associated with cabozantinib in cancer patients

The efficacy of cabozantinib has attracted interest in various solid tumors. The primary aim of this study was to evaluate the risk of hepatotoxicity associated with cabozantinib in the patients with cancer. PubMed, Cochrane, and EMBASE databases were searched for published randomized controlled trials (RCTs) from inception to September 9, 2023. The mainly outcomes were all-grade and grade ≥3 elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), expressed as relative risk (RR) and 95% confidence interval (CI). All data were pooled using fixed-effect or random-effects models according to the heterogeneity of the included RCTs. Among the 922 records identified, 8 RCTs incorporating 2613 patients with cancer were included. For patients receiving cabozantinib, the relative risks of all-grade AST elevation (RR, 2.63; 95% CI, 2.16-3.20, P < 0.001), all-grade ALT elevation (RR, 2.89; 95% CI, 2.31-3.60, P < 0.001), grade ≥3 AST elevation (RR, 2.26; 95% CI, 1.34-3.83, P = 0.002), and grade ≥3 ALT elevation (RR, 3.40; 95% CI, 1.65-7.01, P < 0.001) were higher than those of patients who did not receive cabozantinib group. Further subgroup analysis showed that the relative risk of hepatotoxicity associated with cabozantinib was higher than that in the other TKIs (erlotinib, sunitinib, and sorafenib) and the non-TKI drug groups (everolimus, prednisone, mitoxantrone, and paclitaxel). Compared with other solid tumor drugs, such as everolimus, sorafenib, sunitinib, paclitaxel, mitoxantrone-prednisone et al., cabozantinib has a higher risk of hepatotoxicity.