Systemic therapy for advanced pheochromocytoma and paraganglioma: real-world evidence from a single-center cohort

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine neoplasms characterized by heterogeneous clinical and genetic profiles. Evidence regarding the efficacy of systemic therapies in this population remains limited. We retrospectively reviewed 157 PPGL patients treated at our center between 2021 and 2024. Clinical, pathological, genetic, and treatment data were collected. Outcomes of targeted therapy, chemotherapy, and somatostatin analogs (SSAs) were analyzed, including progression-free survival (PFS). We found that among the 113 patients who underwent next-generation sequencing, 47.8% harbored pathogenic variant, with SDHB being the most frequent. In the overall cohort, median PFS for targeted therapy, chemotherapy, and SSAs was 8.02, 5.06, and 16.03 months, respectively. For the most frequently used agents in each category - surufatinib, temozolomide-based chemotherapy, and lanreotide - median PFS was 13.08, 10.05, and 19.02 months, respectively (P = 0.46). In the first-line setting, targeted therapy and SSAs demonstrated superior efficacy compared with chemotherapy (median PFS 20.01 and 15.05 vs 4.07 months; P < 0.05), with no significant difference observed between surufatinib and lanreotide. In patients with SDHx pathogenic variant versus SDHx normal patient, the mPFS with lanreotide was 15.05 vs 22.05 months and, with temozolomide chemotherapy, was 11.01 vs 7.04 months; neither comparison showed a statistically significant difference. In the first-line setting, targeted therapy and SSAs were associated with longer PFS than chemotherapy, with surufatinib and lanreotide showing favorable disease control. SDHx pathogenic variant status did not show a clear association with response to TKIs or temozolomide, underscoring the need for validation in larger cohorts.