3974 - 177Lu-DOTATATE plus 166Ho-radioembolization in patients with neuroendocrine tumours; a single center, prospective, interventional, non-comparative, open label, phase II study (HEPAR PLUS study)

Background

The liver is the most commonly affected organ in metastatic neuroendocrine disease and is the most incriminating factor for patient survival. Additional treatment of liver disease with radioembolization may improve outcome in NET patients with bulky residual liver disease after PRRT. To investigate this hypothesis, a phase II study was initiated to assess effectiveness and toxicity of holmium-166 radioembolization (¹⁶⁶Ho-RE) after PRRT with lutetium-177 (¹⁷⁷Lu)-DOTATATE.

Methods

The HEPAR PLUS study was a single center, prospective, interventional, non-comparative, open label study. Thirty patients with >3 measurable residual liver metastases according to RECIST 1.1 received ¹⁶⁶Ho-RE within 20 weeks after the 4^th and last cycle of PRRT with 7.4 GBq ¹⁷⁷Lu-DOTATATE. Primary objectives: objective response rate (ORR = complete plus partial response) after three months according to RECIST 1.1 (treatment volume, liver and patient-based analysis). Secondary endpoints included toxicity profile according to CTCAE v4.03 and quality of life assessments according to EORTC QLQ-C30 and GI.NET21 questionnaires.

Results

Three months after PRRT plus ¹⁶⁶Ho-RE, liver ORR was 43% according to RECIST 1.1. In patient-based analysis, ORR was 40% according to RECIST 1.1, stable disaese in 50% and three patient (10%) experienced progressive disease (due to progressive lesions or development of new lesions outside the treatment volume). CTCAE grade 3-4 toxicities were limited to abdominal pain (10%), nausea (3%) and fatigue (3%). One related serious adverse event occurred in one patient (3%), fatal radiation induced liver disease. Quality of life assessments showed a temporary non-significant decrease in most scales at three weeks post-treatment and complete resolution three months after treatment.

Conclusions

This was the first prospective study to combine PRRT and ¹⁶⁶Ho-RE in metastatic NET. A radiation boost on intrahepatic disease using ¹⁶⁶Ho-RE leads to a high objective response rate without significant additional short-term side-effects, and a temporary non-significant decrease in quality of life in well-selected patients.

Clinical trial identification

NCT02067988.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A.J.A.T. Braat: Non-remunerated activity/ies: Terumo; Non-remunerated activity/ies: BTG; Non-remunerated activity/ies: Sirtex Medical. M.G.E.H. Lam: Honoraria (institution), Non-remunerated activity/ies: Terumo; Advisory / Consultancy, Non-remunerated activity/ies: BTG; Advisory / Consultancy, Non-remunerated activity/ies: Sirtex Medical; Non-remunerated activity/ies: Mirada. All other authors have declared no conflicts of interest.