TKI therapy may improve survival in metastatic pheochromocytomas/paragangliomas

Treatment with tyrosine kinase inhibitors (TKIs), such as sunitinib, provides survival benefits to patients with metastatic pheochromocytomas/paragangliomas (PPGLs), suggests a recent study.

A team of investigators searched the databases of PubMed, Cochrane Library, Scopus, Clinical Trial, and Embase using synonyms of 48 TKIs and metastatic PPGLs from inception up to August 2022. They assessed outcomes such as tumour response or survival data and the incidence of adverse events (AEs) after treatment.

Risk of bias was assessed using the MIONRS scale and the JBI’s tools for case series for interventional and observational studies, respectively. The investigators then reported the combined effects with fixed- or random-effect models, then combined median with the weighted median of medians method, and their 95 percent confidence intervals (CIs).

Seven studies including 160 patients were included in the meta-analysis. In five studies with available data, tumour responses in metastatic PPGLs showed a pooled proportion of 0.320 (95 percent CI, 0.155‒0.486) for partial response (PR), 0.520 (95 percent CI, 0.409‒0.630) for stable disease, and 0.856 (95 percent CI, 4.1‒13.5) for disease control rate (DCR).

In six studies, the combined median progression-free survival was 8.9 months (95 percent CI, 4.1‒13.5). In addition, the proportion of patients who stopped using TKIs due to AEs in five studies was 0.143 (95 percent CI, 0.077‒0.209).

“This meta-analysis suggests that patients with metastatic PPGLs can benefit from TKI therapy with PR and DCR up to more than 30 percent and 80 percent, [respectively],” the investigators said. “However, because of restricted studies, larger clinical trials should be performed in the future.”

The National Comprehensive Cancer Network guidelines in 2022 recommended TKIs for the treatment of locally unresectable or distantly metastatic PPGLs.