(TKIs), shows a new systematic review and meta-analysis.
The study, which was published online in JAMA Network Open, found that ICIs were associated with fewer serious adverse events, such as death, illness requiring hospitalization or illness leading to disability.
The findings are based on a meta-analysis of 30 randomized clinical trials and 12,921 patients. The analysis found a greater frequency of serious adverse events among those treated with TKIs than those treated with ICIs, though the rates of less serious liver-related adverse events were similar.
“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 authors wrote.
Most newly diagnosed cases of HCC are unresectable, which leads to palliative treatment. When disease is advanced, systemic treatment is generally chosen, and new options introduced in the past decade have boosted survival. Many of these approaches feature ICIs and TKIs.
HCC therapy continues to evolve, with targeted surgical and locoregional therapies like ablation and embolization, and it’s important to understand how side effects from ICIs and TKIs might impact follow-on procedures.
Neoadjuvant therapy can avoid delays to adjuvant chemotherapy that might occur due to surgical complications. Neoadjuvant therapy also has the potential to downstage the disease from advanced to resectable, and it can provide greater opportunity for patient selection based on both tumor biology and patient characteristics.
However, advanced HCC is a complicated condition. Patients typically have cirrhosis and require an adequate functional liver remnant. Neoadjuvant locoregional treatment has been studied in HCC. A systematic review of 55 studies found no significant difference in disease-free or overall survival between preoperative or postoperative transarterial chemoembolization in resectable HCC. There is some weak evidence that locoregional therapies may achieve downstaging or maintain candidacy past 6 months.
The median age of participants was 62 years. Among the included studies, on average, 84% of patients were male. The mean fraction of patients with disease originating outside the liver was 61%, and the mean percentage with microvascular invasion was 28%. A mean of 82% had stage C according to Barcelona Clinic Liver Center staging.
21% of patients who received TKIs (95% confidence interval, 16%-26%) experienced liver toxicities versus 24% (95% CI, 13%-35%) of patients receiving ICIs. Severe adverse events were more common with TKIs, with a frequency of 46% (95% CI, 40%-51%), compared with 24% of those who received ICIs (95% CI, 13%-35%).
TKIs other than sorafenib were associated with higher rates of severe adverse events (risk ratio, 1.24; 95% CI, 1.07-1.44). ICIs and sorafenib had similar rates of liver toxic effects and severe adverse events.
The study has some limitations, including variations within the included studies in the way adverse events were reported, and there was variation in the inclusion criteria.