Efficacy and safety of sunitinib in treatment of advanced or metastatic pheochromocytomas and paragangliomas: A meta-analysis of sunitinib-treated arms from prospective clinical trials

CONTEXT: Metastatic pheochromocytomas and paragangliomas (mPPGLs) are rare neuroendocrine tumors with limited treatment options. Among the options for the treatment of mPPGLs are tyrosine kinase inhibitors (TKIs), including cabozantinib and sunitinib. However, TKIs have different molecular targets and side effects. Additionally, the evidence supporting their use for these tumors has been limited and of low-quality. OBJECTIVE: To summarize prospective efficacy and safety outcomes of sunitinib among patients with mPPGLs. METHODS: A literature search was conducted to investigate the effects of sunitinib on progression-free survival (PFS) tumor responses and adverse events (AEs) in prospective studies of sunitinib for mPPGLs treatment. Because only one included study had a comparator, quantitative synthesis was performed at the sunitinib-treatment-arm level. RESULTS: Three prospective clinical trials were included in the meta-analysis. The total sample in these studies was 114 patients given sunitinib. The objective response rate was 21.2% (95% CI, 11.7-35.3%), and all the responses were partial, with no complete responses. The stable disease rate was 51.8% (95% CI, 36.8-66.4%). The progressive disease rate was 27.1% (95% CI, 19.5-36.3%). The 12-month PFS rate was 48.2% (95% CI, 38.1-58.5%). The median PFS duration was 11.9 months (95% CI, 6.9-16.9 months). The rate of treatment discontinuation due to AEs was 13.2% (95% CI, 8.1-20.7%). The rate of grade ≥3 adverse events was 57.8% (95% CI, 36.7-76.4%), with substantial heterogeneity (I2 = 86%; P = .001). CONCLUSIONS: Overall, the available low to very low certainty but prospective evidence suggests that sunitinib provides clinically relevant disease control in a subset of patients, characterized by modest objective response rates.