PMID- 32907500 OWN - NLM STAT- MEDLINE DCOM- 20211126 LR - 20211126 IS - 1557-9077 (Electronic) IS - 1050-7256 (Linking) VI - 31 IP - 4 DP - 2021 Apr TI - Donafenib in Progressive Locally Advanced or Metastatic Radioactive Iodine-Refractory Differentiated Thyroid Cancer: Results of a Randomized, Multicenter Phase II Trial. PG - 607-615 LID - 10.1089/thy.2020.0235 [doi] AB - Background: An unmet need for more effective and affordable kinase inhibitors remains in patients with progressive radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) in China, where only sorafenib is approved for this indication. This study evaluated the 24-week objective response rate (ORR) to donafenib-a new, domestic multikinase inhibitor-in the treatment of locally advanced or metastatic RAIR-DTC in patients with measurable lesions. Two dose regimens (300 mg twice daily vs. 200 mg twice daily) were used to determine its optimal dosage and safety for further phase III studies. Methods: This study was a randomized, open-label, multicenter phase II trial. Thirty-five adult RAIR-DTC patients with at least one measurable targeted lesion according to RECIST 1.1 were enrolled from 12 centers in China and randomized to receive either 200 mg (17 patients) or 300 mg (18 patients) of donafenib orally twice daily for 24 weeks. The primary endpoint was ORR, and the secondary endpoints included progression-free survival (PFS) among others. Additionally, biochemical (serum thyroglobulin) and structural (total tumor diameter [TTD]) responses were assessed, change (DeltaTTD) rates were calculated, and safety was evaluated. Results: The ORRs for the 200- and 300-mg arms were 12.5% and 13.33% (p = 1.000), respectively. The 300-mg arm had a nonsignificant, longer median PFS than the 200-mg arm (14.98 months vs. 9.44 months) (p = 0.351). There was a trend toward more tumor shrinkage in the 300-mg arm compared with the 200-mg arm (average DeltaTTD rate -0.52 +/- 0.71 vs. -0.04 +/- 1.55 mm/month, p = 0.103). Most treatment-related adverse events (AEs) in both arms were grades 1-2. The most common grade 3 treatment-related AEs in both arms were palmar-plantar erythrodysesthesia and hypertension; the sum occurrence rates of these two AEs in the 200-mg and 300-mg arms were 11.43% and 22.86%, respectively. Conclusions: Donafenib was generally well tolerated. Both donafenib regimens demonstrated similar efficacy in terms of the ORR in locally advanced or metastatic RAIR-DTC. The results warrant further studies on donafenib as a new, feasible treatment option for RAIR-DTC patients. Clinical Trials.gov IDs: NCT02870569; CTR20160220. FAU - Lin, Yan-Song AU - Lin YS AD - Department of Nuclear Medicine, Peking Union Medical College Hospital, Beijing, China. FAU - Yang, Hui AU - Yang H AD - Department of Nuclear Medicine, Henan Cancer Hospital, Zhengzhou, China. FAU - Ding, Yong AU - Ding Y AD - Department of Nuclear Medicine, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China. FAU - Cheng, Yi-Zhuang AU - Cheng YZ AD - Department of Nuclear Medicine, Anhui Provincial Hospital, Hefei, China. FAU - Shi, Feng AU - Shi F AD - Internal Medicine Department of Thyroid and Radionuclide Therapy, Hunan Cancer Hospital, Changsha, China. FAU - Tan, Jian AU - Tan J AD - Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, China. FAU - Deng, Zhi-Yong AU - Deng ZY AD - Department of Nuclear Medicine, Yunnan Cancer Hospital, Kunming, China. FAU - Chen, Zhen-Dong AU - Chen ZD AD - Department of Oncology, The Second Hospital of Anhui Medical University, Hefei, China. FAU - Wang, Rong-Fu AU - Wang RF AD - Department of Nuclear Medicine, Peking University First Hospital, Beijing, China. FAU - Ji, Qing-Hai AU - Ji QH AD - Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. FAU - Huang, Rui AU - Huang R AD - Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu, China. FAU - Li, Lin-Fa AU - Li LF AD - Department of Nuclear Medicine, Zhejiang Cancer Hospital, Hangzhou, China. LA - eng SI - ClinicalTrials.gov/NCT02870569 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20201015 PL - United States TA - Thyroid JT - Thyroid : official journal of the American Thyroid Association JID - 9104317 RN - 0 (Antineoplastic Agents) RN - 0 (Iodine Radioisotopes) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Pyridines) RN - 0 (Radiopharmaceuticals) RN - 41XGO0VS1U (donafenib) SB - IM MH - Administration, Oral MH - Adult MH - Aged MH - Antineoplastic Agents/*administration & dosage/adverse effects MH - Cell Differentiation MH - China MH - Disease Progression MH - Drug Administration Schedule MH - Female MH - Humans MH - Iodine Radioisotopes/*therapeutic use MH - Male MH - Middle Aged MH - Progression-Free Survival MH - Protein Kinase Inhibitors/*administration & dosage/adverse effects MH - Pyridines/*administration & dosage/adverse effects MH - *Radiation Tolerance MH - Radiopharmaceuticals/*therapeutic use MH - Thyroid Neoplasms/*drug therapy/pathology MH - Time Factors MH - Young Adult OTO - NOTNLM OT - donafenib OT - locally advanced or metastatic OT - multikinase inhibitor OT - phase II trial OT - radioactive iodine-refractory differentiated thyroid cancer EDAT- 2020/09/11 06:00 MHDA- 2021/11/27 06:00 CRDT- 2020/09/10 05:25 PHST- 2020/09/11 06:00 [pubmed] PHST- 2021/11/27 06:00 [medline] PHST- 2020/09/10 05:25 [entrez] AID - 10.1089/thy.2020.0235 [doi] PST - ppublish SO - Thyroid. 2021 Apr;31(4):607-615. doi: 10.1089/thy.2020.0235. Epub 2020 Oct 15.