Lanreotide for Advanced Pheochromocytoma and Paraganglioma: Results of a Multicenter Phase II Trial

Background: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine neoplasms originating from chromaffin cells that express somatostatin receptors (SSTRs) and may therefore be susceptible to somatostatin analogue therapy. Despite this biological rationale, prospective evidence supporting the antiproliferative activity of somatostatin analogues in PPGL is limited. We conducted a multicenter phase 2 clinical trial to assess the efficacy and safety of lanreotide in patients with advanced or metastatic PPGL. [LAMPARA, NCT03946527] Methods: Patients with advanced or metastatic PPGL and evidence of recent disease progression received lanreotide depot/autogel 120 mg subcutaneously every 4 weeks. Treatment was planned for 52 weeks with an option to continue for an additional 52 weeks. Endpoints included overall survival (OS), progression-free survival (PFS), and response according to RECIST. Serum chromogranin A (CgA) was evaluated as an exploratory biomarker. A tumor growth rate analysis was planned to allow comparison with data from the CLARINET trial in gastroenteropancreatic NETs. Results: Eighteen patients (median age 42 years; range 28-77) across three centers participated; 78% carried SDHx mutations. Lanreotide was well tolerated with predominantly grade 1-2 adverse events and no treatment discontinuations due to toxicity. The most common treatment-emergent adverse events were diarrhea (67%), injection-site reaction (44%), constipation (39%), fatigue (39%), and abdominal pain (39%). Serious adverse events were reported in four patients and were assessed as not related or unlikely related to lanreotide. All 18 patients had at least one recorded post-baseline tumor assessment. Two partial responses were recorded during extended follow-up. At approximately 1 year, disease stabilization was observed in 11 of 13 patients (85%) with an available assessment, while two patients (15%) had progressive disease. Biomarker analysis showed substantial variability in serum CgA values. Tumor growth rate analysis revealed a median growth rate of 0.00124/day (tumor doubling time 559 days), comparable in order of magnitude to the rate of 0.00046/day observed in 83 lanreotide-treated patients in CLARINET, and consistent with a median PFS [≥]2 years. Conclusions: Lanreotide exhibits promising antiproliferative activity in PPGL, with a favorable safety profile and extended periods of disease stabilization. These findings support the consideration of SSAs as an option in managing SSTR-positive PPGLs, delaying more aggressive treatments until disease progression mandates escalation.