RADTHYR: an open-label, single-arm, prospective multicenter phase II trial of Radium-223 for the treatment of bone metastases from radioactive iodine refractory differentiated thyroid cancer

Désirée Deandreis (1, 2, 3, 4) , Aline Maillard (1, 5, 2, 6) , Slimane Zerdoud (7) , Claire Bournaud (8) , Lavinia Vija (7) , Christophe Sajous (8) , Marie Terroir (1, 2, 4) , Laurence Leenhardt (9, 10) , Martin Schlumberger (1, 2) , Isabelle Borget (1, 2, 5, 11) , Sophie Leboulleux (1, 2, 4)

1 IGR - Institut Gustave Roussy
2 Université Paris-Saclay
3 UNITO - Università degli studi di Torino = University of Turin
4 Médecine nucléaire
5 CESP - Centre de recherche en épidémiologie et santé des populations
6 SBE - Service de biostatistique et d'épidémiologie
7 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
8 HCL - Hospices Civils de Lyon
9 CIC-BTi - Centre d'investigation clinique Biothérapie [CHU Pitié-Salpêtrière]
10 SU FM - Sorbonne Université - Faculté de Médecine
11 Direction de la recherche clinique [Gustave Roussy]

Purpose: This is the first prospective trial evaluating the efficacy of alpha emitter Radium-223 in patients with bone metastases from radioactive iodine (RAI) refractory (RAIR) differentiated thyroid cancer. Methods: RADTHYR is a multicenter, single-arm prospective Simon two-stage phase II trial (NCT02390934). The primary objective was to establish the efficacy of three administrations of 55 kBq/kg of Radium-223 by 18F-FDG PET/CT according to PERCIST criteria. Secondary objectives were to establish the efficacy of six administrations of Radium-223 by 18F-FDG PET/CT, 99mTc-HMDP bone scan and 18FNa PET/CT, clinical benefits, changes in serum bone markers, thyroglobulin levels, and safety. Results: Ten patients were enrolled between July 2015 and December 2017 (4 M; median age 74 years). Prior to Radium-223 administration, patients received a median RAI cumulative activity of 15 GBq (7.4-35.6), external radiation therapy (n = 9), bone surgery (n = 8), cimentoplasty (n = 5), and cryoablation (n = 2). 18F-FDG PET/CT showed stable disease (SD) in 4/10 and progressive disease (PD) in 6/10 cases after three administrations and SD in 4/10, PD in 5/10 cases, and 1/10 non-evaluable (NE) case after six administrations. After six injections, 99mTc-HMDP bone scan showed SD in 9 cases and was NE in 1 case; 18FNa PET/CT showed SD in 8 cases, partial response (PR) in 1 case, and was NE in 1 case. No significant clinical benefits were reported during the study. A skeletal event occurred in 6 patients (median time without skeletal event of 12.1 months). Seventy-seven adverse events were reported during treatment (7 of grade 3-4). Three patients developed an acute myeloid, a promyelocytic, and a chronic myeloid leukemia after the last Radium-223 administration considered as drug-related. Conclusion: The trial was stopped after interim analysis for lack of response of bone metastases from RAIR thyroid cancer to Radium-223. Severe hematological toxicity was observed in patients heavily pretreated with RAI and external radiation.

Mots clés: Alpha emitters; Bone metastases; Leukemia; Radium-223; Refractory thyroid cancer

Domaines: Sciences du Vivant [q-bio]

Désirée Deandreis, Aline Maillard, Slimane Zerdoud, Claire Bournaud, Lavinia Vija, et al.. RADTHYR: an open-label, single-arm, prospective multicenter phase II trial of Radium-223 for the treatment of bone metastases from radioactive iodine refractory differentiated thyroid cancer. European Journal of Nuclear Medicine and Molecular Imaging, 2021, ⟨10.1007/s00259-021-05229-y⟩. ⟨hal-03151236⟩