Hepatic adverse events with CDK4/6 inhibitors: a systematic review combining meta-analysis and FAERS database.
Yuyao Tang, Yongxin Li, Chengrong Zhang et al.
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In 30 seconds
This systematic review and meta-analysis examined hepatic adverse events associated with CDK4/6 inhibitors in patients with breast cancer, combining 20 randomized controlled trials involving 24,342 patients with an analysis of 400 FAERS cases. Across trials, CDK4/6 inhibitors were associated with higher odds of hepatotoxicity than controls (OR = 1.76, 95%CI 1.40-2.22, I 2 = 75%). Palbociclib, ribociclib, and abemaciclib showed significant hepatotoxicity, whereas dalpiciclib did not. FAERS signals were detected for liver enzyme and organ toxicity with ribociclib and abemaciclib, but not palbociclib.
Key findings
- Across 20 RCTs, CDK4/6 inhibitors were associated with increased hepatotoxicity versus controls (OR = 1.76, 95%CI 1.40-2.22, I 2 = 75%).
- Palbociclib, ribociclib, and abemaciclib showed significant hepatotoxicity in the trial analysis; dalpiciclib did not.
- FAERS analysis identified liver enzyme and organ toxicity signals for ribociclib and abemaciclib, but not palbociclib.
- Elevated ALT and AST were the most common reported manifestations.
Why it matters
The findings indicate that hepatic adverse events are relevant when CDK4/6 inhibitors are used with endocrine therapy for breast cancer. Differences in trial results and FAERS signals across agents may help frame safety discussions and attention to liver-related adverse events, while the evidence does not establish that every reported signal represents a causal effect.
What to keep in mind
The meta-analysis showed substantial heterogeneity (I 2 = 75%). FAERS is a spontaneous-reporting database, so its signals do not establish incidence or causality.