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Immune Checkpoint and Tyrosine Kinase Inhibitors in Hepatocellular Carcinoma: Comparison of Toxicity Profiles

By: Cordi Craig, MS
Posted: Friday, September 30, 2022

Over the past decade, new options for targeted systemic therapy for hepatocellular carcinoma have evolved for patients with advanced disease, and survival results have improved significantly with both tyrosine kinase inhibitors and immune checkpoint inhibitors. Pablo E. Serrano, MD, MPH, of McMaster University, Hamilton, Ontario, Canada, and colleagues performed a meta-analysis to explore the toxicity profiles of neoadjuvant therapies; many surgeons are concerned that the adverse events of such therapies may lead to delays or cancellations in surgeries. The report was published in JAMA Network Open.

“When considering objective response rates, combination therapy with atezolizumab and bevacizumab or lenvatinib alone likely offer the most promise in the neoadjuvant setting in terms of objective response and toxic effects without preventing patients from reaching surgery,” the investigators stated.

The meta-analysis included 30 prospective clinical trials including nearly 13,000 patients with hepatocellular carcinoma. The mean age of patients was 62 years. The primary outcome was the proportion of patients with clinically significant liver-related adverse events. The secondary outcomes included relevant adverse events (grade 3 or higher) and significant adverse events that were life-threatening, required hospitalization, or caused prolonged disability.

Patients treated with immune checkpoint inhibitors reported fewer serious adverse events than patients who received tyrosine kinase inhibitors (24% vs. 46%, respectively). Overall, 28% of patients treated with tyrosine kinase inhibitors had toxic liver effects, compared with 21% of patients who received immune checkpoint inhibitors. Compared with those patients who received sorafenib, patients who were treated with other tyrosine kinase inhibitors had similar rates of liver toxic effects but higher rates of severe adverse events. Patients who were treated with immune checkpoint inhibitors had similar rates of liver toxic effects and severe adverse events as those patients treated with sorafenib.

Disclosure: For full disclosures of the study authors, visit jamanetwork.com.


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