Endocrine Abstracts

JOINT255

Introduction: Metastatic pheochromocytomas and paragangliomas (mPPGLs) are rare neuroendocrine tumors with a variable treatment response. A new radioligand therapy (RLT), a radiolabelled somatostatin receptor antagonist (¹⁷⁷Lu-DOTA-JR11) which use has proven high efficacy in patients with NETs G1-G3, may offer increased tumor doses compared to standard RLT with 177Lu-DOTA-TOC in patients with mPPGLs which express somatostatin receptor subtype 2.

Aim: The main objective was to evaluate the tumor absorbed dose of ¹⁷⁷Lu-DOTA-JR11 and ¹⁷⁷Lu-DOTA-TOC in the same patients with progressive mPPGLs, non-responsive to conventional treatment. Secondary objectives included efficacy and safety assessment of ¹⁷⁷Lu-DOTA-JR11 in these patients.

Material and methods: We retrospectively retrieved data of 6 patientswith mPPGLs, treated with 1-2 cycles ¹⁷⁷Lu-DOTA-TOC at a standard injected activity of 7.4 GBq followed in an interval of 10-12 months by one cycle ¹⁷⁷Lu-DOTA-JR11 (2 GBq/m² × body surface area). Tumor absorbed doses were computed using the 75 keV-window for 161Tb and the 208 keV-window for ¹⁷⁷Lu as well as the Monte-Carlo-based OSEM algorithm. Therapy efficacy was expressed as progression free survival (PFS) before and after ¹⁷⁷Lu-DOTA-JR11, symptoms control and hormonal marker response. Safety was assessed as possible adverse events associated to¹⁷⁷Lu-DOTA-JR11.

Results: Six patients (4 women; 3 PHEOs, 3 PGLs) with a median age at diagnosis of 38 (25-65), a median age when receiving first ¹⁷⁷Lu-DOTA-JR11 cycle of 57 (45-75) years and a Ki-67 between 7 and 30% were included. The median tumor absorbed dose of ¹⁷⁷Lu-DOTA-JR11 was higher compared to standard ¹⁷⁷Lu-DOTA-TOC (D=7.9 (1.1-12.1) vs. 3.7 (1.3-10.6) Gy/cycle, respectively). After one cycle of ¹⁷⁷Lu-DOTA-JR11 with a median injected activity of 3.6 GBq (2.8-4.3 GBq), patients had a higher PFS [9 (4-17) months] than before ¹⁷⁷Lu-DOTA-JR11 start [6 (2-11) months], at a median follow-up duration of 28 months. Two out of 3 patients with functional tumor were free of adrenergic symptoms after treatment. ChromograninA decreased less than baseline levels after > 3 months posttreatment in 2/4 (50%) patients. The most reported adverse events were anemia grade 2 (n= 3, 50%), lymphocytopenia grade 2 and 3 (n= 3, 50%), followed by hypoalbuminemia grade 1 (n= 2, 33%). There weren’t grade 4 or 5 events, thrombocytopenia or neutropenia and no kidney or liver disfunction.

Conclusion: This pilot study on mPGGLsshowed that the median tumor absorbed dose per cycle is 1.3 (0.9-3.5) times higher with ¹⁷⁷Lu-DOTA-JR11 compared to ¹⁷⁷Lu-DOTA-TOC, resulting in a longer PFS and a good clinical outcome without relevant adverse events after ¹⁷⁷Lu-DOTA-JR11 therapy.