Eyun Song1, Mijin Kim2, Eui Young Kim3, Bo Hyun Kim2, Dong Yeob Shin4, Ho-Cheol Kang5, Byeong-Cheol Ahn6, Won Bae Kim1, Young Kee Shong1, Min Ji Jeon1, Dong Jun Lim7. 1. Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. 2. Division of Endocrinology and Metabolism, Department of Internal Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea. 3. Department of Endocrinology, Dongnam Institute of Radiological and Medical Sciences Cancer Center, Busan, Republic of Korea. 4. Division of Endocrinology and Metabolism, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. 5. Division of Endocrinology and Metabolism, Department of Internal Medicine, Chonnam National University Hwasun Hospital, Chonnam, Republic of Korea. 6. Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea. 7. 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.
Abstract
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 (TGSpre, p = 0.003) and after (TGSpost, 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 (TVDTpre, p = 0.923) or after (TVDTpost, 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.
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 (TGSpre, p = 0.003) and after (TGSpost, 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 (TVDTpre, p = 0.923) or after (TVDTpost, 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.
Authors: Anne Christine Kaae; Michael C Kreissl; Marcus Krüger; Manfred Infanger; Daniela Grimm; Markus Wehland Journal: Int J Mol Sci Date: 2021-11-12 Impact factor: 5.923
Authors: Thomas Crezee; Marika H Tesselaar; Martin Jaeger; Katrin Rabold; Willem E Corver; Hans Morreau; Adriana C H Van Engen-Van Grunsven; Jan W A Smit; Romana T Netea-Maier; Theo S Plantinga Journal: Oncol Lett Date: 2021-06-06 Impact factor: 2.967