PRRT plus holmium-166-SIRT (HEPAR PLuS) versus PRRT-only in patients with metastatic neuroendocrine tumors: A...

Patients with bulky neuroendocrine liver metastases (NELM) undergoing PRRT with [¹⁷⁷Lu]Lu-DOTATATE have a worse survival than patients with limited liver metastases. Previously, the safety and efficacy of additional selective internal radiotherapy (SIRT), using holmium-166 (¹⁶⁶Ho)-microspheres, directly following PRRT in patients with NELM were confirmed in the prospective HEPAR PLuS study. The aim of the current study was to provide insight into the efficacy and survival benefit of PRRT + ¹⁶⁶Ho-SIRT over PRRT-only by means of a propensity score matched historical cohort. A multicenter retrospective data collection was performed to match patients treated with PRRT-only to the prospectively collected HEPAR PLuS study patients. Demographic, clinical, laboratory, and imaging data were collected. The primary endpoint was the proportion of patients with progression-free survival (PFS) at 2 years after the start of PRRT. Secondary endpoints included the proportion of patients with 2-year hepatic PFS (hPFS), general PFS and hPFS, objective response rates (ORR), and overall survival (OS). Twenty-four patients were 1:1 matched and included in the analysis. All key matching criteria were balanced between cohorts if feasible. The proportion of patients with PFS and hPFS at 2 years was 68% and 82% after PRRT + ¹⁶⁶Ho-SIRT versus 55% and 50% after PRRT only. Time to median PFS was comparable (31 vs. 30 months). An initial delay in hepatic progression or death of any cause was observed in PRRT + ¹⁶⁶Ho-SIRT mNET patients (75% probability of PFS at 27 vs. 22 months), most notably in intestinal tumors (75% probability of PFS at 26 vs. 15 months). Best ORR was 71% after PRRT + ¹⁶⁶Ho-SIRT versus 25% after PRRT only. This study showed that ¹⁶⁶Ho-SIRT after PRRT (vs. PRRT-only) had a positive effect on the liver disease progression in patients with NELM, increasing the 2-year hPFS rate and tumor response and delaying hepatic progression or death. However, this effect did not translate into improving general PFS and OS.