THE ADDED VALUE OF 166HO TRANS-ARTERIAL RADIOEMBOLIZATION TO SYSTEMIC THERAPY IN LIVER METASTATIC BREAST CANCER PATIENTS

Liver metastases occur in approximately 50% of the metastatic breast cancer
patients and are an independent negative prognostic factor for OS. Most LMBC
patients have extended systemic disease and will therefore receive systemic
therapy. Challenges of chemotherapy remain the toxicity levels and resistance
which necessitate a switch or a break of chemotherapeutical. When patients
become resistant to systemic therapy and have liver metastasis, they may
benefit from an intra-arterial therapy, such as TARE. The available literature
for TARE in LMBC patients is however more limited with mainly retrospective or
small prospective series. Nevertheless, these reports show promising results
with a pooled response rate of 49% (range 9-100%) and a pooled median survival
of 9.2 months (range 6.1-35.4 months). The longest OS after TARE to date was
reached in the study that combined 90Y TARE with systemic therapy in 83% of the
patients. Yet, two out of the four serious adverse events occurred in the
patients that concurrently received pembrolizumab and carboplatin. Therefore,
safety of the combination of TARE and systemic therapy should be evaluated
first before moving into an efficacy trial. The current available evidence for
TARE in LMBC patients is mainly built with 90Y microspheres. 166Ho
microspheres have recently become available in the European market as the third
type of microspheres for radioembolization. 166Ho has specific imaging and
treatment benefits over 90Y TARE which can potentially enhance the results of
this treatment in unresectable liver metastases. To date, only small numbers of
LMBC patients are treated with 166Ho radioembolization.
We hypothesize that the addition of 166Ho TARE to systemic chemotherapy can
enhance the response rate of liver metastatic breast cancer patients after
failed initial systemic chemotherapy with an acceptable toxicity level.

We aim to introduce 166Ho radioembolization combined with systemic chemotherapy
and investigate its safety and feasibility.

Multicenter clinical pilot study.

Patients start with their newly selected chemotherapy. If no extra-hepatic
tumour progression is seen after their chemotherapy evaluation of the newly
selected therapy, she can be screened for inclusion. A blood sample is taken
and a liver MRI, and a mapping angiography will be performed to evaluate if she
is suitable for radioembolization. If she is suitable for TARE and meets the
inclusion criteria she can be included. The radioembolization will be performed
within two weeks after the mapping angiography. Chemotherapy needs to be
stopped 2-5 weeks prior to TARE and can be continued after two weeks at
earliest.

We expect that the addition of 166Ho TARE to systemic chemotherapy can enhance
the response rate a of liver metastatic breast cancer patients and eventually
improve survival in this patient population. It is expected that the combined
use of systemic chemotherapy and TARE has an increased but acceptable toxicity
over the use of systemic chemotherapy alone. With our strict inclusion criteria
we try to select a group of patients that is less prone for toxicity. The
toxicity will be an endpoint of this study. Patients need to visit the hospital
6 times extra for this study and have to fill in three Quality of life forms.
Two extra blood samples will be taken and two MRI's of the liver will be
performed. The screenings investigations and the actual treatment are included
in these 6 extra hospital visits. These procedures are minimal invasive and
will be performed at most under local anesthesia.