A phase 2 study of lanreotide as a therapy for pheochromocytomas (PCs) and paragangliomas (PGs).

10612 Background: PCs arise from adrenomedullary chromaffin cells, while PGs are derived from extra-adrenal chromaffin cells of the sympathetic paravertebral ganglia of the thorax, abdomen, and pelvis, or the parasympathetic ganglia located along the glossopharyngeal and vagal nerves in the neck and base of skull. Although considered neuroendocrine tumors [NETs] by many, their rarity and often difficult management has meant they’re never included in clinical trials of NETs. And while they express somatostatin receptors [SSTRs] comparable to other NETs haven’t been managed with SSTR-antagonists. Methods: Conducted clinical trial to assess efficacy/toxicity of Somatuline Depot / Lanreotide Autogel every 4 weeks in patients with advanced/metastatic PC/PG. Evidence of recent disease progression while either not receiving any therapy or receiving a therapy deemed ineffective was required. Treatment planned for 52 weeks with option to continue for additional 52 weeks. Endpoints included OS, PFS and response according to RECIST. Additionally given rarity of these cancers, estimates of tumor growth rates were planned to allow comparisons to data in NETs enrolled in CLARINET. Results: Eighteen patients median age 42 years enrolled including 11 females and 7 males of whom 13 were white, 2 black, 3 other. 14/18 had an SDHx mutation. Prior therapies included surgery, RT, chemotherapy, and PRRT. Lanreotide was well tolerated with 68%G1, 26%G2, 6.5%G3 and < 1%G4 adverse events (AEs) and no unexpected toxicities. No patient discontinued treatment for AEs. Blood pressure control uneventful. Ten patients completed two years of lanreotide, three ongoing, two discontinued at one year due to burden of traveling for participation and three had PD. RECIST response at one year was 15 SD, and 3 PD. One additional patient had PD at the two-year assessment. Serum chromogranin was elevated in only 4/18 and was not helpful in assessing response. With a median follow up of 40 months, median PFS exceeds 2 years with only three deaths to date 14, 18 and 52 months after enrollment. Rates of tumor growth and regression could be assessed in 16/18 patients. Growth was not detected in 5/16 but estimable in 11/16 with a median growth rate of 0.00067/day [tumor doubling time, 1034 days] compared to rate of 0.00046 for 83 patients treated with lanreotide in CLARINET. Conclusions: These data demonstrate efficacy for lanreotide in the treatment of PC/PG comparable to that previously found in NETs with prolonged disease stability the primary outcome. Given emerging data with PC and PG reports limited efficacy for Lutathera with meaningful toxicity, these data with lanreotide achieving a longer median PFS support a management strategy for PC/PG similar to that employed with NETs. Begin with a SSTR antagonist, extract its benefit and delay Lutathera administration until meaningful, consistent disease progression is documented. Clinical trial information: NCT03946527 .