PMID- 31910091 OWN - NLM STAT- MEDLINE DCOM- 20210604 LR - 20210604 IS - 1557-9077 (Electronic) IS - 1050-7256 (Linking) VI - 30 IP - 5 DP - 2020 May TI - Lenvatinib for Radioactive Iodine-Refractory Differentiated Thyroid Carcinoma and Candidate Biomarkers Associated with Survival: A Multicenter Study in Korea. PG - 732-738 LID - 10.1089/thy.2019.0476 [doi] AB - Background: Lenvatinib, an oral multikinase inhibitor, is the latest addition to the treatment options for radioactive iodine (RAI)-refractory progressive differentiated thyroid carcinoma (DTC). This study investigated the efficacy of lenvatinib in real-world practice and prognostic biomarkers of survival. Methods: This multicenter study included 43 patients receiving lenvatinib as first-line or second-line treatment after sorafenib for RAI-refractory DTC. Progression-free survival (PFS) was evaluated according to various clinical factors including thyroglobulin doubling time (TgDT), tumor volume DT (TVDT), and tumor growth slope (TGS; slope of tumor change rate). Results: Patients were treated with lenvatinib for a median of 14 months; 32 were previously treated with sorafenib. The median follow-up from lenvatinib initiation to the last censoring or death was 16 months. The median starting dose of 20 mg was reduced to a median sustainable dose of 10 mg in accordance with patient adverse events (AEs). The median PFS was 21.8 months; the median overall survival was not reached. The disease control rate was 97.7%, with the first objective response at 3.8 months. PFS was not significantly associated with previous sorafenib treatment, metastatic sites, or sustainable dose. TGS measured before (TGS(pre), p = 0.003) and after (TGS(post), p = 0.036) the initiation of lenvatinib was associated with PFS. The sum of the largest diameters of target lesions (p = 0.043) and TgDT (p = 0.024) were associated with PFS, but TVDT calculated before (TVDT(pre), p = 0.923) or after (TVDT(post), p = 0.966) lenvatinib treatment did not impact PFS. Lenvatinib was withdrawn in 24 patients (55.8%): in 6 patients because of treatment-induced AEs and in 18 patients because of disease progression or poor performance status. AEs of any grade were reported in all patients, and grade 3-4 AEs in 23.2% of the patients. The most frequent AE was fatigue or asthenia. Conclusions: Our results indicate that reduced doses of lenvatinib triggered by emergent AEs did not abrogate its apparent efficacy in patients with RAI-refractory DTCs. Rather, the sustained use of reduced doses of lenvatinib with a low rate of severe AEs may have contributed to the favorable outcomes. TgDT and TGS can assist in predicting the outcomes in these patients. FAU - Song, Eyun AU - Song E AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. FAU - Kim, Mijin AU - Kim M AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea. FAU - Kim, Eui Young AU - Kim EY AD - Department of Endocrinology, Dongnam Institute of Radiological and Medical Sciences Cancer Center, Busan, Republic of Korea. FAU - Kim, Bo Hyun AU - Kim BH AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea. FAU - Shin, Dong Yeob AU - Shin DY AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. FAU - Kang, Ho-Cheol AU - Kang HC AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Chonnam National University Hwasun Hospital, Chonnam, Republic of Korea. FAU - Ahn, Byeong-Cheol AU - Ahn BC AD - Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea. FAU - Kim, Won Bae AU - Kim WB AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. FAU - Shong, Young Kee AU - Shong YK AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. FAU - Jeon, Min Ji AU - Jeon MJ AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. FAU - Lim, Dong Jun AU - Lim DJ AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20200211 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 (Phenylurea Compounds) RN - 0 (Quinolines) RN - EE083865G2 (lenvatinib) SB - IM MH - Aged MH - Antineoplastic Agents/*therapeutic use MH - Female MH - Humans MH - Iodine Radioisotopes/therapeutic use MH - Male MH - Middle Aged MH - Phenylurea Compounds/*therapeutic use MH - Progression-Free Survival MH - Quinolines/*therapeutic use MH - Republic of Korea MH - Retreatment MH - Survival Rate MH - Thyroid Neoplasms/*drug therapy/mortality/radiotherapy MH - Treatment Outcome OTO - NOTNLM OT - lenvatinib OT - progression-free survival OT - radioiodine-refractory differentiated thyroid carcinoma EDAT- 2020/01/08 06:00 MHDA- 2021/06/05 06:00 CRDT- 2020/01/08 06:00 PHST- 2020/01/08 06:00 [pubmed] PHST- 2021/06/05 06:00 [medline] PHST- 2020/01/08 06:00 [entrez] AID - 10.1089/thy.2019.0476 [doi] PST - ppublish SO - Thyroid. 2020 May;30(5):732-738. doi: 10.1089/thy.2019.0476. Epub 2020 Feb 11.