-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
- Cosmetic Ingredient
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
Introduction For patients with differentiated thyroid cancer (DTC), after tumor recurrence or metastasis, it is easy to develop radioiodine-resistant DTC (RAIR-DTC)
.
The treatment options for RAIR-DTC are relatively limited, and the patient's prognosis is poor, which is a difficulty in the treatment of DTC
.
The "2021 Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Differentiated Thyroid Cancer" (hereinafter referred to as the "Guide") absorbs the latest developments in the field of thyroid cancer based on China's national conditions, and provides the latest authority for the diagnosis and treatment of Chinese patients Evidence supports 1
.
Yimaitong specially invited Professor Guo Ye from Dongfang Hospital of Tongji University to interpret the systematic treatment part of the 2021 edition of the "Guide"
.
Expert profileProfessor Guo YeDeputy Director of the Department of Cancer Medicine and Director of the Phase I Clinical Center of the Oriental Hospital Affiliated to Tongji University Deputy Secretary-General of the Chinese Society of Clinical Oncology Chairman of the Head and Neck Tumor Expert Committee of the Chinese Society of Clinical Oncology Member of the Standing Committee of the Lymphoma Alliance of the Chinese Society of Clinical Oncology Thyroid of the Chinese Society of Clinical Oncology Vice Chairman of the Cancer Expert Committee Vice Chairman of the Head and Neck Tumor Professional Committee of the Chinese Medical Doctor Association Vice Chairman of the Lymphoma Professional Committee of the Chinese Geriatric Health Association Member, Chinese Anti-Cancer Association Nasopharyngeal Cancer Professional Committee Member, Chinese Anti-Cancer Association Lymphoma Professional Committee Member, Shanghai Anti-Cancer Association Lymphoma Professional Committee Secretary-General, Shanghai Anti-Cancer Association Head and Neck Tumor Professional Committee Deputy Chairman, 2021 version of the "Guide" Proposed the specific concept of RAIR-DTC 1: In the absence of interference from exogenous iodine load, in the state of thyroid-stimulating hormone (TSH) stimulation (>30mIU/L), DTC patients after standard 131I treatment have the following One of the situations can be defined as RAIR-DTC: ①The lesions show no iodine uptake on the whole body imaging after 131I treatment, and they cannot benefit from subsequent 131I treatment (if too much residual thyroid gland may affect the imaging of metastases) Iodine can be evaluated when re-treatment after nail ablation); ②The original iodine-intake lesions gradually lose iodine uptake ability after 131I treatment; ③Some lesions in the same patient take iodine, and some lesions do not take iodine, and there is no biochemical relief; ④Iodine was taken in the lesion, but the disease progressed within 1 year; ⑤The cumulative dose of 131I exceeded 600mCi, but the disease did not relieve
.
If it is judged to be RAIR-DTC, the following treatment options can be considered: Table 1 Systematic Treatment Guidelines Recommended Guidelines Recommendation: If the patient is asymptomatic and the disease is stable or slowly progressing, regular follow-up can be considered.
For RAIR-DTC, if the patient is asymptomatic and the disease is stable or slowly progressing, regular follow-up every 3-6 months is a reasonable choice.
There is currently no evidence that starting systemic treatment early can help improve overall survival1
.
Guidelines recommend: For patients with symptoms or rapid disease progression, systemic treatment should be performed.
Interpretation 1: For patients with positive RET fusion genes, specific RET inhibitors, DTC, especially papillary thyroid carcinoma (PTC), should be selected for less than 10%.
% Of patients have the RET fusion gene, and the incidence of thyroid cancer in China is 8.
5%
.
This "Guide" included RET fusion gene detection into the pathological diagnosis recommendation for the first time (level II recommendation)
.
The most common partner genes of RET are CCDC 6 and NCOA4
.
DTC patients with RET fusion gene can consider specific RET inhibitors such as pratinib
.
In the global multicenter ARROW clinical study2, patients with RET-fused iodine-refractory DTC and advanced RET mutant MTC were included.
The results showed that pratinib treated RET-fused iodine-refractory DTC with an objective response rate (ORR) of 89 %, all patients had tumor shrinkage, and the remission time was more than 6 months, and the median time to first remission was 1.
9 months
.
The 6-month and 12-month remission rates are expected to be 100% and 86%, respectively
.
The median duration of response (DOR) and median progression-free survival (PFS) were not reached
.
The objective remission rates of pratinib for initial treatment and treated RET mutant MTC were 71% and 60%, respectively
.
Figure 1 The maximum reduction of target lesions of pratinib in the treatment of RET-fusion-iodine refractory DTC patients.
Pratinib is well tolerated in the treatment of RET variant thyroid cancer.
There are no new adverse reactions in the Chinese population, and no patients have treatment-related adverse events.
Event (TRAEs) and stop treatment or die
.
Based on the results of the ARROW study, the U.
S.
Food and Drug Administration (FDA) approved pratinib in December 2020 for the treatment of iodine-refractory RET fusion thyroid cancer and RET-mutated advanced medullary thyroid cancer for 12 years and older.
.
The National Medical Products Administration (NMPA) of China has accepted relevant indications and has been included in the priority review1,2
.
Interpretation 2: For patients with RET fusion gene negative or unknown DTC, anti-vascular small molecule multi-target kinase inhibitors can be used, and in a few cases, the chemotherapeutic drug adriamycin can be considered.
Level I expert recommendation: lenvatinib (category 1A), Rafenib (category 1A): Sorafenib was approved in China in March 2017 for the treatment of iodine-refractory relapsed and metastatic DTC
.
The DECISION study showed that Sorafenib significantly improved ORR (12% vs 0.
5%) and PFS (10.
8 months vs 5.
8 months) compared with placebo, but there was no significant difference in OS
.
Figure 2 PFS of sorafenib in the treatment of iodine-refractory relapsed and metastatic DTC In November 2020, lenvatinib was approved in China for the treatment of iodine-refractory relapsed and metastatic DTC
.
The SELECT study showed4 that compared with placebo, lenvatinib significantly improved ORR (64.
8% vs 1.
5%) and PFS (18.
3 months vs 3.
6 months), but OS had no significant benefit
.
Figure 3 The PFS of lenvatinib in the treatment of iodine-refractory relapsed and metastatic DTC.
In the DECISION and SELECT clinical studies, the most common (≥50%) adverse events were hypertension, diarrhea, weight loss and fatigue
.
For intolerable toxicity, it is usually necessary to suspend the administration or reduce the dose, and a small number of patients need to terminate the treatment
.
There is currently a lack of randomized controlled studies of sorafenib and lenvatinib.
However, in view of the higher tumor remission rate and lower risk of disease progression of lenvatinib, ESMO and NCCN guidelines both preferentially recommend lenvatinib1
.
Level II expert recommendation: Apatinib (category 1B), Anlotinib (category 1B) Apatinib is the first domestically developed anti-vascular small molecule multi-target kinase inhibitor
.
The results of the REALITY study showed that the ORR of apatinib in the treatment of iodine-refractory relapsed and metastatic DTC was 54.
3%, and the median PFS and OS were better than placebo
.
The results of a phase II randomized controlled clinical study of Anlotinib in the treatment of iodine-refractory relapsed and metastatic DTC showed that the ORR was 59.
2%, PFS was significantly better than the placebo group, and OS was obtained after adjusting for the effect of cross-treatment.
Benefit
.
At present, neither apatinib nor anlotinib has been approved for the treatment of RAIR-DTC in China
.
Level III expert recommendation: Adriamycin (category 2B) For patients with symptoms or rapid disease progression, chemotherapy can only be considered in a few cases
.
Doxorubicin is the only recommended drug1
.
Table 2 Summary of information on targeted drugs for refractory, recurrent and metastatic differentiated thyroid cancer with radioactive iodine References: 1.
Chinese Society of Clinical Oncology Guidelines Working Committee.
Chinese Society of Clinical Oncology (CSCO) Guidelines for Diagnosis and Treatment of Differentiated Thyroid Cancer (2021) ［M］.
People's Medical Publishing House 2.
Subbiah V, Hu MI, Wirth LJ, et al.
Pralsetinib for patients with advanced or metastatic RET-altered thyroid cancer (ARROW): a multi-cohort, open-label, registrational, phase 1/2 study [J].
Lancet Diabetes Endocrinol.
2021 Aug;9(8):491-501.
3.
Brose MS, Nutting CM, Jarzab B, et al.
Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer : a randomised, double-blind, phase 3 trial [J].
Lancet.
2014 Jul 26;384(9940):319-28.
4.
Schlumberger M, Tahara M, Wirth LJ, et al.
Lenvatinib versus placebo in radioiodine-refractory thyroid cancer [J].
N Engl J Med.
2015 Feb 12;372(7):621-30.
5.
Lin YS,Qin SK,Li ZY,et al.
A randomized multicentered phase III study to evaluate apatinib in subjects with locally advanced or metastatic radioactive iodine-refractory differentiated thyroid cancer [J].
Ann Oncol, 2020,21(suppl_6):S1142.
6.
Chi M,Gao Y,Zhang Y, et al.
Anlotinib in locally advanced or metastatic radioiodine-refractory differentiated thyroid carcinoma: A randomized, double-blind, multicenter phase II trial [J].
Ann Oncol 2020,31(suppl_6): S1347.
.
The treatment options for RAIR-DTC are relatively limited, and the patient's prognosis is poor, which is a difficulty in the treatment of DTC
.
The "2021 Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Differentiated Thyroid Cancer" (hereinafter referred to as the "Guide") absorbs the latest developments in the field of thyroid cancer based on China's national conditions, and provides the latest authority for the diagnosis and treatment of Chinese patients Evidence supports 1
.
Yimaitong specially invited Professor Guo Ye from Dongfang Hospital of Tongji University to interpret the systematic treatment part of the 2021 edition of the "Guide"
.
Expert profileProfessor Guo YeDeputy Director of the Department of Cancer Medicine and Director of the Phase I Clinical Center of the Oriental Hospital Affiliated to Tongji University Deputy Secretary-General of the Chinese Society of Clinical Oncology Chairman of the Head and Neck Tumor Expert Committee of the Chinese Society of Clinical Oncology Member of the Standing Committee of the Lymphoma Alliance of the Chinese Society of Clinical Oncology Thyroid of the Chinese Society of Clinical Oncology Vice Chairman of the Cancer Expert Committee Vice Chairman of the Head and Neck Tumor Professional Committee of the Chinese Medical Doctor Association Vice Chairman of the Lymphoma Professional Committee of the Chinese Geriatric Health Association Member, Chinese Anti-Cancer Association Nasopharyngeal Cancer Professional Committee Member, Chinese Anti-Cancer Association Lymphoma Professional Committee Member, Shanghai Anti-Cancer Association Lymphoma Professional Committee Secretary-General, Shanghai Anti-Cancer Association Head and Neck Tumor Professional Committee Deputy Chairman, 2021 version of the "Guide" Proposed the specific concept of RAIR-DTC 1: In the absence of interference from exogenous iodine load, in the state of thyroid-stimulating hormone (TSH) stimulation (>30mIU/L), DTC patients after standard 131I treatment have the following One of the situations can be defined as RAIR-DTC: ①The lesions show no iodine uptake on the whole body imaging after 131I treatment, and they cannot benefit from subsequent 131I treatment (if too much residual thyroid gland may affect the imaging of metastases) Iodine can be evaluated when re-treatment after nail ablation); ②The original iodine-intake lesions gradually lose iodine uptake ability after 131I treatment; ③Some lesions in the same patient take iodine, and some lesions do not take iodine, and there is no biochemical relief; ④Iodine was taken in the lesion, but the disease progressed within 1 year; ⑤The cumulative dose of 131I exceeded 600mCi, but the disease did not relieve
.
If it is judged to be RAIR-DTC, the following treatment options can be considered: Table 1 Systematic Treatment Guidelines Recommended Guidelines Recommendation: If the patient is asymptomatic and the disease is stable or slowly progressing, regular follow-up can be considered.
For RAIR-DTC, if the patient is asymptomatic and the disease is stable or slowly progressing, regular follow-up every 3-6 months is a reasonable choice.
There is currently no evidence that starting systemic treatment early can help improve overall survival1
.
Guidelines recommend: For patients with symptoms or rapid disease progression, systemic treatment should be performed.
Interpretation 1: For patients with positive RET fusion genes, specific RET inhibitors, DTC, especially papillary thyroid carcinoma (PTC), should be selected for less than 10%.
% Of patients have the RET fusion gene, and the incidence of thyroid cancer in China is 8.
5%
.
This "Guide" included RET fusion gene detection into the pathological diagnosis recommendation for the first time (level II recommendation)
.
The most common partner genes of RET are CCDC 6 and NCOA4
.
DTC patients with RET fusion gene can consider specific RET inhibitors such as pratinib
.
In the global multicenter ARROW clinical study2, patients with RET-fused iodine-refractory DTC and advanced RET mutant MTC were included.
The results showed that pratinib treated RET-fused iodine-refractory DTC with an objective response rate (ORR) of 89 %, all patients had tumor shrinkage, and the remission time was more than 6 months, and the median time to first remission was 1.
9 months
.
The 6-month and 12-month remission rates are expected to be 100% and 86%, respectively
.
The median duration of response (DOR) and median progression-free survival (PFS) were not reached
.
The objective remission rates of pratinib for initial treatment and treated RET mutant MTC were 71% and 60%, respectively
.
Figure 1 The maximum reduction of target lesions of pratinib in the treatment of RET-fusion-iodine refractory DTC patients.
Pratinib is well tolerated in the treatment of RET variant thyroid cancer.
There are no new adverse reactions in the Chinese population, and no patients have treatment-related adverse events.
Event (TRAEs) and stop treatment or die
.
Based on the results of the ARROW study, the U.
S.
Food and Drug Administration (FDA) approved pratinib in December 2020 for the treatment of iodine-refractory RET fusion thyroid cancer and RET-mutated advanced medullary thyroid cancer for 12 years and older.
.
The National Medical Products Administration (NMPA) of China has accepted relevant indications and has been included in the priority review1,2
.
Interpretation 2: For patients with RET fusion gene negative or unknown DTC, anti-vascular small molecule multi-target kinase inhibitors can be used, and in a few cases, the chemotherapeutic drug adriamycin can be considered.
Level I expert recommendation: lenvatinib (category 1A), Rafenib (category 1A): Sorafenib was approved in China in March 2017 for the treatment of iodine-refractory relapsed and metastatic DTC
.
The DECISION study showed that Sorafenib significantly improved ORR (12% vs 0.
5%) and PFS (10.
8 months vs 5.
8 months) compared with placebo, but there was no significant difference in OS
.
Figure 2 PFS of sorafenib in the treatment of iodine-refractory relapsed and metastatic DTC In November 2020, lenvatinib was approved in China for the treatment of iodine-refractory relapsed and metastatic DTC
.
The SELECT study showed4 that compared with placebo, lenvatinib significantly improved ORR (64.
8% vs 1.
5%) and PFS (18.
3 months vs 3.
6 months), but OS had no significant benefit
.
Figure 3 The PFS of lenvatinib in the treatment of iodine-refractory relapsed and metastatic DTC.
In the DECISION and SELECT clinical studies, the most common (≥50%) adverse events were hypertension, diarrhea, weight loss and fatigue
.
For intolerable toxicity, it is usually necessary to suspend the administration or reduce the dose, and a small number of patients need to terminate the treatment
.
There is currently a lack of randomized controlled studies of sorafenib and lenvatinib.
However, in view of the higher tumor remission rate and lower risk of disease progression of lenvatinib, ESMO and NCCN guidelines both preferentially recommend lenvatinib1
.
Level II expert recommendation: Apatinib (category 1B), Anlotinib (category 1B) Apatinib is the first domestically developed anti-vascular small molecule multi-target kinase inhibitor
.
The results of the REALITY study showed that the ORR of apatinib in the treatment of iodine-refractory relapsed and metastatic DTC was 54.
3%, and the median PFS and OS were better than placebo
.
The results of a phase II randomized controlled clinical study of Anlotinib in the treatment of iodine-refractory relapsed and metastatic DTC showed that the ORR was 59.
2%, PFS was significantly better than the placebo group, and OS was obtained after adjusting for the effect of cross-treatment.
Benefit
.
At present, neither apatinib nor anlotinib has been approved for the treatment of RAIR-DTC in China
.
Level III expert recommendation: Adriamycin (category 2B) For patients with symptoms or rapid disease progression, chemotherapy can only be considered in a few cases
.
Doxorubicin is the only recommended drug1
.
Table 2 Summary of information on targeted drugs for refractory, recurrent and metastatic differentiated thyroid cancer with radioactive iodine References: 1.
Chinese Society of Clinical Oncology Guidelines Working Committee.
Chinese Society of Clinical Oncology (CSCO) Guidelines for Diagnosis and Treatment of Differentiated Thyroid Cancer (2021) ［M］.
People's Medical Publishing House 2.
Subbiah V, Hu MI, Wirth LJ, et al.
Pralsetinib for patients with advanced or metastatic RET-altered thyroid cancer (ARROW): a multi-cohort, open-label, registrational, phase 1/2 study [J].
Lancet Diabetes Endocrinol.
2021 Aug;9(8):491-501.
3.
Brose MS, Nutting CM, Jarzab B, et al.
Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer : a randomised, double-blind, phase 3 trial [J].
Lancet.
2014 Jul 26;384(9940):319-28.
4.
Schlumberger M, Tahara M, Wirth LJ, et al.
Lenvatinib versus placebo in radioiodine-refractory thyroid cancer [J].
N Engl J Med.
2015 Feb 12;372(7):621-30.
5.
Lin YS,Qin SK,Li ZY,et al.
A randomized multicentered phase III study to evaluate apatinib in subjects with locally advanced or metastatic radioactive iodine-refractory differentiated thyroid cancer [J].
Ann Oncol, 2020,21(suppl_6):S1142.
6.
Chi M,Gao Y,Zhang Y, et al.
Anlotinib in locally advanced or metastatic radioiodine-refractory differentiated thyroid carcinoma: A randomized, double-blind, multicenter phase II trial [J].
Ann Oncol 2020,31(suppl_6): S1347.
