Lenvatinib in the treatment of locally advanced thyroid cancer: a single-center prospective clinical study_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LIANG Yanwen ,  WU Yu

Department of Head and Neck Surgery, Fujian Cancer Hospital, Clinical Oncology School of Fujian Medical University, Fuzhou 350000, P. R. China;

Corresponding author：

WU Yu, Email: 429146964@qq.com

Keywords：

locally advanced thyroid cancer; lenvatinib; targeted therapy; efficacy; safety

DOI：

10.7507/1007-9424.202404054

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To evaluate the safety and efficacy of lenvatinib as targeted therapy for locally advanced thyroid cancer. Methods The data of patients with locally advanced thyroid cancer including details on therapy dosage, treatment outcomes and drug-related adverse events who received targeted therapy in the Department of Head and Neck Surgery, Clinical Oncology School of Fujian Medical University from September 2021 to June 2023 were collected and analyzed. Results Seventeen patients received lenvatinib for a median of 8 weeks (range, 4–32 weeks). The objective response and disease control rates were 29.4% (5/17) and 94.1% (16/17) respectively. Five patients did not undergo surgery because of tumor progression and their refusal; R0/1 resection was achieved in eleven of the twelve remaining patients (91.7%). The commonest drug-related adverse events were hypertension (7/17, 41.2%), diarrhea (6/17, 35.3%), and proteinuria (5/17, 29.4%). There were no major treatment-related adverse events. Conclusion Preliminary analysis indicates that lenvatinib is effective and safe for targeted therapy of locally advanced thyroid cancer, with a relatively high rate of R0/1 resection.

1.	Hay ID, Thompson GB, Grant CS, et al. Papillary thyroid carcinoma managed at the Mayo Clinic during six decades (1940-1999): temporal trends in initial therapy and long-term outcome in 2 444 consecutively treated patients. World J Surg, 2002, 26(8): 879-885.
2.	Shindo ML, Caruana SM, Kandil E, et al. Management of invasive well-differentiated thyroid cancer: an American Head and Neck Society consensus statement. AHNS consensus statement. Head Neck, 2014, 36(10): 1379-1390.
3.	Urken ML, Haser GC, Likhterov I, et al. The impact of metastatic lymph nodes on risk stratification in differentiated thyroid cancer: have we reached a higher level of understanding? Thyroid, 2016, 26(4): 481-488.
4.	Lim H, Devesa SS, Sosa JA, et al. Trends in thyroid cancer incidence and mortality in the United States, 1974-2013. JAMA, 2017, 317(13): 1338-1348.
5.	Glaser SM, Mandish SF, Gill BS, et al. Anaplastic thyroid cancer: prognostic factors, patterns of care, and overall survival. Head Neck, 2016, 38 Suppl 1: E2083-E2090.
6.	Schlumberger M, Tahara M, Wirth LJ, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med, 2015, 372(7): 621-630.
7.	Dierks C, Seufert J, Aumann K, et al. Combination of lenvatinib and pembrolizumab is an effective treatment option for anaplastic and poorly differentiated thyroid carcinoma. Thyroid, 2021, 31(7): 1076-1085.
8.	管小青, 郑向欣, 顾书成, 等. 多学科团队在晚期特殊类型甲状腺癌诊治中的应用价值. 中国普外基础与临床杂志, 2018, 25(9): 1115-1120.
9.	Fallahi P, Ferrari SM, Galdiero MR, et al. Molecular targets of tyrosine kinase inhibitors in thyroid cancer. Semin Cancer Biol, 2022, 79: 180-196.
10.	Higashiyama T, Sugino K, Hara H, et al. Phase Ⅱ study of the efficacy and safety of lenvatinib for anaplastic thyroid cancer (HOPE). Eur J Cancer, 2022, 173: 210-218.
11.	Takahashi S, Kiyota N, Yamazaki T, et al. A phase Ⅱ study of the safety and efficacy of lenvatinib in patients with advanced thyroid cancer. Future Oncol, 2019, 15(7): 717-726.
12.	Zheng X, Xu Z, Ji Q, et al. A randomized, phase Ⅲ study of lenvatinib in Chinese patients with radioiodine-refractory differentiated thyroid cancer. Clin Cancer Res, 2021, 27(20): 5502-5509.
13.	Huang NS, Wei WJ, Xiang J, et al. The efficacy and safety of anlotinib in neoadjuvant treatment of locally advanced thyroid cancer: a single-arm phase Ⅱ clinical trial. Thyroid, 2021, 31(12): 1808-1813.
14.	St Bernard R, Zheng L, Liu W, et al. Fibroblast growth factor receptors as molecular targets in thyroid carcinoma. Endocrinology, 2005, 146(3): 1145-1153.
15.	Costa R, Carneiro BA, Chandra S, et al. Spotlight on lenvatinib in the treatment of thyroid cancer: patient selection and perspectives. Drug Des Devel Ther, 2016 Feb 29: 10: 873-84.10-873.
16.	Besic N, Auersperg M, Dremelj M, et al. Neoadjuvant chemotherapy in 16 patients with locally advanced papillary thyroid carcinoma. Thyroid, 2013, 23(2): 178-184.
17.	Brose MS, Panaseykin Y, Konda B, et al. A randomized study of lenvatinib 18 mg vs 24 mg in patients with radioiodine-refractory differentiated thyroid cancer. J Clin Endocrinol Metab, 2022, 107(3): 776-787.
18.	Kim M, Ahn J, Song DE, et al. Real-world experience of lenvatinib in patients with advanced anaplastic thyroid cancer. Endocrine, 2021, 71(2): 427-433.
19.	Sukumar JS, Moore W, Khan SA. Therapy with tyrosine kinase inhibitor lenvatinib in radioactive iodine-naive advanced differentiated thyroid cancer. International Journal of Endocrine Oncology, 2019, 6(4): IJE23.
20.	Tahara M, Brose MS, Wirth LJ, et al. Impact of dose interruption on the efficacy of lenvatinib in a phase 3 study in patients with radioiodine-refractory differentiated thyroid cancer. Eur J Cancer, 2019, 106: 61-68.
21.	Masaki C, Sugino K, Saito N, et al. Efficacy and limitations of lenvatinib therapy for radioiodine-refractory differentiated thyroid cancer: real-world experiences. Thyroid, 2020, 30(2): 214-221.
22.	Taylor MH, Takahashi S, Capdevila J, et al. Correlation of performance status and neutrophil-lymphocyte ratio with efficacy in radioiodine-refractory differentiated thyroid cancer treated with lenvatinib. Thyroid, 2021, 31(8): 1226-1234.
23.	Brauckhoff M, Machens A, Thanh PN, et al. Impact of extent of resection for thyroid cancer invading the aerodigestive tract on surgical morbidity, local recurrence, and cancer-specific survival. Surgery, 2010, 148(6): 1257-1266.
24.	Gaissert HA, Honings J, Grillo HC, et al. Segmental laryngotracheal and tracheal resection for invasive thyroid carcinoma. Ann Thorac Surg, 2007, 83(6): 1952-1959.
25.	McCaffrey JC. Aerodigestive tract invasion by well-differentiated thyroid carcinoma: diagnosis, management, prognosis, and biology. Laryngoscope, 2006, 116(1): 1-11.
26.	Hartl DM, Zago S, Leboulleux S, et al. Resection margins and prognosis in locally invasive thyroid cancer. Head Neck, 2014, 36(7): 1034-1038.
27.	Maurer E, Eilsberger F, Wächter S, et al. Mutation-based, short-term “neoadjuvant” treatment allows resectability in stage ⅣB and C anaplastic thyroid cancer. Eur Arch Otorhinolaryngol, 2023, 280(3): 1509-1518.
28.	Russell M, Gild ML, Wirth LJ, et al. Neoadjuvant therapy to improve resectability of advanced thyroid cancer: a real-world experience. Head Neck, 2024 Mar 15. doi: 10.1002/hed.27735.
29.	Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1. 1). Eur J Cancer, 2009, 45(2): 228-247.
30.	Brauckhoff M, Machens A, Thanh PN, et al. Impact of extent of resection for thyroid cancer invading the aerodigestive tract on surgical morbidity, local recurrence, and cancer-specific survival. Surgery, 2010, 148(6): 1257-1266.
31.	Gaissert HA, Honings J, Grillo HC, et al. Segmental laryngotracheal and tracheal resection for invasive thyroid carcinoma. Ann Thorac Surg, 2007, 83(6): 1952-1959.
32.	Wirth LJ, Tahara M, Robinson B, et al. Treatment-emergent hypertension and efficacy in the phase 3 Study of (E7080) lenvatinib in differentiated cancer of the thyroid (SELECT). Cancer, 2018, 124(11): 2365-2372.
33.	谭宇珊, 刘枫. 碘难治性分化型甲状腺癌靶向治疗研究进展. 中国普外基础与临床杂志, 2023, 30(9): 1130-1137.
34.	McCrary HC, Aoki J, Huang Y, et al. Mutation based approaches to the treatment of anaplastic thyroid cancer. Clin Endocrinol (Oxf), 2022, 96(5): 734-742.

1. Hay ID, Thompson GB, Grant CS, et al. Papillary thyroid carcinoma managed at the Mayo Clinic during six decades (1940-1999): temporal trends in initial therapy and long-term outcome in 2 444 consecutively treated patients. World J Surg, 2002, 26(8): 879-885.
2. Shindo ML, Caruana SM, Kandil E, et al. Management of invasive well-differentiated thyroid cancer: an American Head and Neck Society consensus statement. AHNS consensus statement. Head Neck, 2014, 36(10): 1379-1390.
3. Urken ML, Haser GC, Likhterov I, et al. The impact of metastatic lymph nodes on risk stratification in differentiated thyroid cancer: have we reached a higher level of understanding? Thyroid, 2016, 26(4): 481-488.
4. Lim H, Devesa SS, Sosa JA, et al. Trends in thyroid cancer incidence and mortality in the United States, 1974-2013. JAMA, 2017, 317(13): 1338-1348.
5. Glaser SM, Mandish SF, Gill BS, et al. Anaplastic thyroid cancer: prognostic factors, patterns of care, and overall survival. Head Neck, 2016, 38 Suppl 1: E2083-E2090.
6. Schlumberger M, Tahara M, Wirth LJ, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med, 2015, 372(7): 621-630.
7. Dierks C, Seufert J, Aumann K, et al. Combination of lenvatinib and pembrolizumab is an effective treatment option for anaplastic and poorly differentiated thyroid carcinoma. Thyroid, 2021, 31(7): 1076-1085.
8. 管小青, 郑向欣, 顾书成, 等. 多学科团队在晚期特殊类型甲状腺癌诊治中的应用价值. 中国普外基础与临床杂志, 2018, 25(9): 1115-1120.
9. Fallahi P, Ferrari SM, Galdiero MR, et al. Molecular targets of tyrosine kinase inhibitors in thyroid cancer. Semin Cancer Biol, 2022, 79: 180-196.
10. Higashiyama T, Sugino K, Hara H, et al. Phase Ⅱ study of the efficacy and safety of lenvatinib for anaplastic thyroid cancer (HOPE). Eur J Cancer, 2022, 173: 210-218.
11. Takahashi S, Kiyota N, Yamazaki T, et al. A phase Ⅱ study of the safety and efficacy of lenvatinib in patients with advanced thyroid cancer. Future Oncol, 2019, 15(7): 717-726.
12. Zheng X, Xu Z, Ji Q, et al. A randomized, phase Ⅲ study of lenvatinib in Chinese patients with radioiodine-refractory differentiated thyroid cancer. Clin Cancer Res, 2021, 27(20): 5502-5509.
13. Huang NS, Wei WJ, Xiang J, et al. The efficacy and safety of anlotinib in neoadjuvant treatment of locally advanced thyroid cancer: a single-arm phase Ⅱ clinical trial. Thyroid, 2021, 31(12): 1808-1813.
14. St Bernard R, Zheng L, Liu W, et al. Fibroblast growth factor receptors as molecular targets in thyroid carcinoma. Endocrinology, 2005, 146(3): 1145-1153.
15. Costa R, Carneiro BA, Chandra S, et al. Spotlight on lenvatinib in the treatment of thyroid cancer: patient selection and perspectives. Drug Des Devel Ther, 2016 Feb 29: 10: 873-84.10-873.
16. Besic N, Auersperg M, Dremelj M, et al. Neoadjuvant chemotherapy in 16 patients with locally advanced papillary thyroid carcinoma. Thyroid, 2013, 23(2): 178-184.
17. Brose MS, Panaseykin Y, Konda B, et al. A randomized study of lenvatinib 18 mg vs 24 mg in patients with radioiodine-refractory differentiated thyroid cancer. J Clin Endocrinol Metab, 2022, 107(3): 776-787.
18. Kim M, Ahn J, Song DE, et al. Real-world experience of lenvatinib in patients with advanced anaplastic thyroid cancer. Endocrine, 2021, 71(2): 427-433.
19. Sukumar JS, Moore W, Khan SA. Therapy with tyrosine kinase inhibitor lenvatinib in radioactive iodine-naive advanced differentiated thyroid cancer. International Journal of Endocrine Oncology, 2019, 6(4): IJE23.
20. Tahara M, Brose MS, Wirth LJ, et al. Impact of dose interruption on the efficacy of lenvatinib in a phase 3 study in patients with radioiodine-refractory differentiated thyroid cancer. Eur J Cancer, 2019, 106: 61-68.
21. Masaki C, Sugino K, Saito N, et al. Efficacy and limitations of lenvatinib therapy for radioiodine-refractory differentiated thyroid cancer: real-world experiences. Thyroid, 2020, 30(2): 214-221.
22. Taylor MH, Takahashi S, Capdevila J, et al. Correlation of performance status and neutrophil-lymphocyte ratio with efficacy in radioiodine-refractory differentiated thyroid cancer treated with lenvatinib. Thyroid, 2021, 31(8): 1226-1234.
23. Brauckhoff M, Machens A, Thanh PN, et al. Impact of extent of resection for thyroid cancer invading the aerodigestive tract on surgical morbidity, local recurrence, and cancer-specific survival. Surgery, 2010, 148(6): 1257-1266.
24. Gaissert HA, Honings J, Grillo HC, et al. Segmental laryngotracheal and tracheal resection for invasive thyroid carcinoma. Ann Thorac Surg, 2007, 83(6): 1952-1959.
25. McCaffrey JC. Aerodigestive tract invasion by well-differentiated thyroid carcinoma: diagnosis, management, prognosis, and biology. Laryngoscope, 2006, 116(1): 1-11.
26. Hartl DM, Zago S, Leboulleux S, et al. Resection margins and prognosis in locally invasive thyroid cancer. Head Neck, 2014, 36(7): 1034-1038.
27. Maurer E, Eilsberger F, Wächter S, et al. Mutation-based, short-term “neoadjuvant” treatment allows resectability in stage ⅣB and C anaplastic thyroid cancer. Eur Arch Otorhinolaryngol, 2023, 280(3): 1509-1518.
28. Russell M, Gild ML, Wirth LJ, et al. Neoadjuvant therapy to improve resectability of advanced thyroid cancer: a real-world experience. Head Neck, 2024 Mar 15. doi: 10.1002/hed.27735.
29. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1. 1). Eur J Cancer, 2009, 45(2): 228-247.
30. Brauckhoff M, Machens A, Thanh PN, et al. Impact of extent of resection for thyroid cancer invading the aerodigestive tract on surgical morbidity, local recurrence, and cancer-specific survival. Surgery, 2010, 148(6): 1257-1266.
31. Gaissert HA, Honings J, Grillo HC, et al. Segmental laryngotracheal and tracheal resection for invasive thyroid carcinoma. Ann Thorac Surg, 2007, 83(6): 1952-1959.
32. Wirth LJ, Tahara M, Robinson B, et al. Treatment-emergent hypertension and efficacy in the phase 3 Study of (E7080) lenvatinib in differentiated cancer of the thyroid (SELECT). Cancer, 2018, 124(11): 2365-2372.
33. 谭宇珊, 刘枫. 碘难治性分化型甲状腺癌靶向治疗研究进展. 中国普外基础与临床杂志, 2023, 30(9): 1130-1137.
34. McCrary HC, Aoki J, Huang Y, et al. Mutation based approaches to the treatment of anaplastic thyroid cancer. Clin Endocrinol (Oxf), 2022, 96(5): 734-742.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Latest ArticlesLenvatinib in the treatment of locally advanced thyroid cancer: a single-center prospective clinical study

Abstract Full text Figures/Tables Video References Cited by

Format

Content