Efficacy of 223Radium in radioactive iodine refractory bone metastases from thyroid cancer: Preliminary results of a single arm Phase II trial

562 Introduction: Radium 223 is indicated for the treatment of symptomatic bone metastases from castration-resistant prostate cancer. The aim of this trial was to evaluate the efficacy of Radium 223 in patients with bone metastases from radioactive iodine (RAI) refractory differentiated thyroid cancer (DTC). Methods: This is a multicenter single arm two-stage Simon Phase II trial (NCT02390934). Primary objective was to establish the efficacy of 3 monthly Radium-223 administrations by FDG PET/CT according to PERCIST criteria in patients with bone metastases from RAI refractory DTC without visceral metastases or with no progressive visceral metastases. Secondary objectives were to establish the efficacy of 6 monthly administrations of Radium-223 by FDG PET/CT according to PERCIST criteria, monthly clinical benefits during treatment, response on 99mTc-HMDP bone scan and 18 NaF PET/CT after 3 and 6 monthly administrations of Radium-223, changes in serum bone markers and thyroglobulin levels during Radium-223 treatment and to assess the safety of Radium-223 according to NCI CTCAE scale version 4. Results: A total of 10 patients were prospectively enrolled between July 2015 and December 2017 (4 M; 6F; Median Age 74 y, range 62-76). Patients presented with Papillary (n=5), Follicular (n=3) and Poorly differentiated TC (n=2). The median interval of time between the initial diagnosis of bone metastases and inclusion was 6 yrs (4-10). Median number of RAI treatments received before Radium 223 was 4 (3-6) with a median cumulated activity of 15 GBq (7-26). The median interval of time between last RAI treatment and inclusion was 3 yrs (1-5). Patients received previously external radiation therapy (n=9), interventional radiology treatment (n=3) and bone surgery (n=8). Nine of the 10 patients received 6 cycles of radium 223, whereas 1 patient stopped Radium 223 after 3 cycles because of urgent surgery for bone skeletal event. PERCIST response at FDG PET after 3 monthly administration of Radium 223 was Stable Disease (SD) in 6/10 cases and Progressive Disease (PD) in 4/10 cases. PERCIST response at FDG PET after 6 monthly administrations in the 9 evaluable patients was SD in 5 cases and PD in 4 case. After 6 cycles of Radium 223, tumor response evaluated with bone scan was SD in 9/9 cases and with 18NaF PET/CT was SD in 8 cases and Partial Response (PR) in 1 case. After 6 cycles of Radium 223 there was not significant decrease in thyroglobulin or alkaline phosphatase (ALP) levels. During the treatment period there was 1 case of grade 3 neutropenia, but 2 patients developed acute myeloid and promyelocitic leukemia respectively during follow up. Conclusions: The trial was stopped after the first step analysis for absence of response to Radium 223 according to PERCIST criteria at FDG PET in patients with bone metastases from RAI refractory DTC. Furthermore awareness of hematological toxicity in case of previously RAI and external radiation therapy is needed.