Responses to systemic therapy in metastatic pheochromocytoma/paraganglioma - A retrospective multi-center cohort study

Abstract Objective The therapeutic options for metastatic pheochromocytomas/paragangliomas (mPPGLs) include chemotherapy with cyclophosphamide/vincristine/dacarbazine (CVD), temozolomide monotherapy, radionuclide therapies, and tyrosine kinase inhibitors such as sunitinib. The objective of this multicenter retrospective study was to evaluate and compare the responses of mPPGLs including those with pathogenic variants in SDHB, to different systemic treatments. Design Retrospective analysis of treatment responses of mPPGL patients (n=74) to systemic therapies. Methods Patients with mPPGLs treated at six specialized national centers were selected based on participation in the ENSAT registry. Survival until detected progression (SDP) and disease-control rates (DCR) at three months were evaluated based on imaging reports. Results For the group of patients with progressive disease at baseline (83.8% of 74 patients), the DCR with first-line CVD chemotherapy was 75.0% (n=4, SDP 11 months; SDHB [n=1]: DCR 100%, SDP 30 months), with somatostatin peptide receptor-based radionuclide therapy (PPRT) 85.7% (n=21, SDP 17 months; SDHB [n=10]: DCR 100%, SDP 14 months), with 131I-meta-iodobenzylguanidine (131I-MIBG) 82.6% (n=23, SDP 43 months; SDHB [n=4]: DCR 100%, SDP 24 months), with sunitinib 100% (n=7, SDP 18 months; SDHB [n=3]: DCR 100%, SDP 18 months) and with somatostatin analogs 100% (n=4, SDP not reached). The DCR with temozolomide as second-line therapy was 60.0% (n=5, SDP 10 months; SDHB [n=4]: DCR 75%, SDP 10 months). Conclusions We demonstrate in a real-life clinical setting that all current therapies show reasonable efficacy in preventing disease progression, and this is equally true for patients with germline SDHB mutations.