Multikinase Inhibitors for the Treatment of Asymptomatic Radioactive Iodine-Refractory Differentiated Thyroid Cancer: Global Noninterventional Study (RIFTOS MKI)

Marcia S. S. Brose*, Johannes W. A. Smit, Chia-Chi Lin, Masayuki Tori, Daniel W. W. Bowles, Francis Worden, Daniel Hueng-Yuan Shen, Shih-Ming Huang, Hui-Jen Tsai, Maria Alevizaki, Robin P. P. Peeters, Shunji Takahashi, Pavel Rumyantsev, Rongjin Guan, Svetlana Babajanyan, Kirhan Ozgurdal, Iwao Sugitani, Fabian Pitoia, Livia Lamartina

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)
33 Downloads (Pure)


Background: Sorafenib and lenvatinib are multikinase inhibitors (MKIs) approved for patients with radioactive iodine-refractory (RAI-R) differentiated thyroid cancer (DTC). There is no consensus on when to initiate MKI treatment. The objective of this study was to evaluate time to symptomatic progression (TTSP) in patients with RAI-R DTC for whom the decision to treat with an MKI was made at study entry. Methods: International, prospective, open-label, noninterventional cohort study (NCT02303444). Eligible patients had asymptomatic progressive RAI-R DTC, with ≥1 lesion ≥1 cm in diameter and life expectancy ≥6 months. The decision to treat with an MKI was at the treating physician's discretion. Primary endpoint was TTSP from study entry. Two cohorts were evaluated: patients for whom a decision to initiate an MKI was made at study entry (Cohort 1) and patients for whom there was a decision not to initiate an MKI at study entry (Cohort 2). Cohorts were compared descriptively. Results: The full analysis set (FAS) comprised 647 patients. The median duration of observation was 35.5 months (range <1-59.4). Of 344 MKI-treated patients, 209 received sorafenib, 191 received lenvatinib, and 19 received another MKI at some point. Median TTSP was 55.4 months (interquartile range [IQR] 18.6-not estimable [NE]) overall, 55.4 months (IQR 15.2-NE) in Cohort 1 (n = 169), and 51.4 months (IQR 20.0-NE) in Cohort 2 (n = 478). TTSP ≥36 months was achieved in 64.5% of patients overall, 59.5% of patients in Cohort 1, and 66.4% of patients in Cohort 2. Median overall survival from classification as RAI-R was 167 months and median progression-free survival from start of MKI therapy was 19.2 months and from start of sorafenib therapy 16.7 months. Among sorafenib-treated patients, 70% had dose modifications, 35% had a dose reduction, 89% experienced ≥1 treatment-emergent adverse event (TEAE), and 82% experienced ≥1 drug-related TEAE. Conclusions: This real-world study provides valuable insight into outcomes in patients with asymptomatic, progressive RAI-R DTC under observation or receiving MKI treatment. TTSP in the FAS provides insight into the current prognosis for patients with RAI-R DTC in the era of MKIs. Registration: NCT02303444.

Original languageEnglish
Pages (from-to)1059-1068
Number of pages10
Issue number9
Publication statusPublished - 14 Sept 2022

Bibliographical note

Funding Information:
The authors thank the patients in the RIFTOS study, their families and the RIFTOS investigators, and participating study centers. The study was sponsored by Bayer HealthCare. Editorial assistance in the preparation of this article was provided by Victoria Jones of OPEN Health Communications (London, UK), with financial support from Bayer.

Publisher Copyright:
ª Mary Ann Liebert, Inc.


Dive into the research topics of 'Multikinase Inhibitors for the Treatment of Asymptomatic Radioactive Iodine-Refractory Differentiated Thyroid Cancer: Global Noninterventional Study (RIFTOS MKI)'. Together they form a unique fingerprint.

Cite this