Outcomes of systemic treatment according to germline mutational status in patients with metastatic pheochromocytoma and paraganglioma

Introduction Metastatic disease affects approximately 15% to 17% of patients with pheochromocytomas and paragangliomas (PPGLs). Unfortunately, treatment options for metastatic PPGLs are limited and rely on small, nonrandomized clinical trials. The impact of germline mutation status on systemic treatment outcomes remains unclear. To address these gaps, we retrospectively evaluated treatment outcomes in patients with PPGL. Patients and Methods Between December 2004 and December 2021, 33 patients were diagnosed with metastatic PPGLs and received systemic treatment at the Department of Oncology, Asan Medical Center, Seoul, South Korea. Results The median age of the patients was 49. Germline mutations were revealed in nine patients (39.1%) out of 23 who underwent germline testing, with SDHB mutation being the most frequent in 5 patients. Cyclophosphamide, vincristine, and dacarbazine (CVD) chemotherapy was administered to 18 patients, with an objective response rate (ORR) of 22% and a disease control rate (DCR) of 67%. The median progression-free survival (PFS) was 7.9 and the median overall survival (OS) was 36.2 months. Sunitinib was given to 6 patients, which had an ORR of 33%, a DCR of 83%, and a median PFS of 14.6 months. Notably, patients with SDHB/SDHD mutation (4 patients and one patient, respectively) who received CVD treatment had a significantly better OS than those without (median OS 94.0 months vs. 13.7 months, P = .01). Conclusion Our study reveals that CVD and sunitinib are effective treatments for metastatic PPGLs. The results are consistent with previous studies and patients with SDHB and SDHD mutations may benefit most from CVD treatment.