Targeted therapies for metastatic pheochromocytoma and paraganglioma: A systematic review and meta-analysis.

Abstract

e16346 Background: Pheochromocytomas and paragangliomas are neuroendocrine tumors that have similar histopathology and clinical course. They also have comparable rates and timing of metastases, with metachronous pattern being more predominant. Currently, there are very limited treatment options for metastatic pheochromocytomas and paragangliomas (MPPGs), especially those that are rapidly progressive. Targeted therapies were recently investigated as possible options for management of these aggressive malignancies. This systematic review and meta-analysis evaluated the efficacy of targeted therapies in patients with MPPGs. Methods: A systematic literature search identified six studies investigating the use of targeted therapies in MPPGs. Five studies covering 109 patients that evaluated the use of cabozantinib, sunitinib, and pazopanib were subsequently included in the meta-analysis. The primary outcome was overall response rate (ORR). Data were pooled using a random-effects meta-analysis. Heterogeneity was assessed using the I 2 statistic and Cochran's Q test. Results: The pooled ORR for all targeted therapies was 0.31 (95% CI: 0.19-0.53), indicating a statistically significant association between targeted therapy and reduced odds of progression in patients with MPPG. Subgroup analysis showed that the pooled ORR for sunitinib was 0.32 (95% CI: 0.16-0.66), 0.11 (95% CI: 0.01-0.88) for pazopanib, and 0.33 (95% CI: 0.11-1.03) for cabozantinib. Heterogeneity across all studies was low (I 2 = 2.9%, p = 0.398). No significant subgroup differences were observed between different therapies (p = 0.8136). Conclusions: This meta-analysis suggests that targeted therapies, particularly sunitinib, may offer a modest clinical benefit for patients with MPPGs. However, the limited sample size and number of studies, particularly for cabozantinib and pazopanib, and the inclusion of single-arm trials, warrant cautious interpretation. Larger randomized controlled trials are needed to confirm these findings.