Basic condition of the patient
Basic situation: In December 2015, the patient underwent total thyroidectomy of the left and right lobes, followed by radioactive iodine therapy
During the follow-up of the disease, it was found that the patient had progressed to the disease and had multiple metastases
in bone, lung and lymph nodes.
Personal history: no history of smoking, alcohol consumption, allergies, or substance abuse
The patient's previous treatment history
On 8 December 2015, the patient underwent total left and right thyroidectomy
Surgical treatment: total left and right lobectomy of the thyroid gland
Postoperative pathological results: follicular carcinoma of the thyroid gland (FTC), differentiation grade unknown
From 12 January 2016 to 16 May 2016, the patient was treated with radioactive iodine
The patient was treated with radioactive iodine and subsequent systemic imaging showed no iodine uptake lesions
Donafenib treatment undergoes
Baseline: height 160cm, weight 67.
2kg, BMI 26.
25kg/m², Eastern Cancer Collaborative Group physical status score (ECOG PS) 0, no previous systemic therapy;
Tumor baseline: T3N1M1, target lesion 15.
3mm, multiple metastases in bone, lung and lymph nodes;
Laboratory baseline: thyroid-stimulating hormone (TSH) 0.
447 mIU/L (local laboratory); Thyroglobulin (Tg) 1446 ng/mL, thyroglobulin antibody (TgAb) 12.
61 IU/mL (central laboratory).
On June 21, 2019, the patient was enrolled in the DIRECTION study and started oral multikinase inhibitor donafenib 300 mg twice
At week 8 of enrollment, the patient achieved partial remission (PR);
The patient was assessed by the Center for Independent Review (IRC) as having a progression-free survival (PFS) of 18.
3 months, with the best overall response to PR.
As of February 28, 2021 (the deadline for study data analysis), patients are still on
Tg levels and TSH levels changed from baseline to day 616 of treatment
Target lesions and overall efficacy changed from baseline to week 88 of treatment
Imaging changes of target lesion 001 in patients during donafenib treatment
Changes in target lesions evaluated by central imaging during donafenib treatment
Changes in target lesions in patients during donafenib treatment
Donafenib treatment-related adverse reactions (TRAE) occur
This case is FTC, and after total thyroidectomy of the left and right lobes, he was treated with radioactive iodine, and subsequent whole-body imaging did not show iodine uptake lesions
On June 21, 2019, after multiple evaluations, the patient met the inclusion criteria for the DIRECTION study and was enrolled in the clinical study
At the 8th week of treatment, the patient's imaging results showed that the disease had reached PR.
As of the time of data analysis, the patient's tumor had been maintained in PR status after the investigator's assessment, and the investigator's PFS was 20.
During the treatment period, no grade > 3 adverse events occurred, and other grade 1 and 2 adverse events were alleviated after symptomatic treatment, indicating that the safety of donafenib is controllable
Professor Ma Qingjie
Department of Nuclear Medicine, China-Japan Union Hospital, Jilin University
FTC is a malignancy of thyroid follicular cell origin with an incidence of approximately 6% to 10%, is more aggressive than papillary thyroid carcinoma (PTC), and is prone to distant metastasis¹
According to statistics, about 25% of FTC patients will have distant metastases, and the common distant metastases are lung, bone, liver, etc.
After 4 months of radioactive iodine treatment, the whole body imaging of the patient in this case did not show iodine uptake of the lesion, indicating that the disease developed to iodine refractory
Although differentiated thyroid cancer (DTC, including FTC and PTC) has a better overall prognosis and lower mortality, the survival of patients with RAIR-DTC is significantly shorter, with an average survival of only 3-5 years and a 10-year survival rate of about 10%²
In addition, the patient has poor prognostic factors
such as bone, lung, and lymph node metastases.
Although the patient had a variety of adverse prognostic factors, the patient quickly reached PR status after 8 weeks of donafenib monotherapy and had an IRC-assessed PFS of 18.
The good benefit for this patient is a "microcosm" of the success of the DIRECTION study, a randomized, double-blind, placebo-controlled, multicenter phase III study to evaluate the efficacy and safety
of the deuterated drug donafenib in Chinese patients with RAIR-DTC 。 The results of the study showed that donafenib significantly prolonged mPFS in patients with RAIR-DTC (IRC assessment: 12.
9 versus 6.
4 months, HR=0.
0001), and subgroup analysis showed that donafenib was able to prolong mPFS for 10.
9 months in patients with RAIR-DTC who were not treated with TKI (18.
3 vs 7.
4 months, HR=0.
45, 95% CI 0.
73), For patients with RAIR-DTC who had previously received TKI, the trend of benefit was more pronounced in the donafenib group (11.
0 vs 3.
7 months, HR = 0.
227, 95% CI 0.
085 to 0.
In terms of compliance and safety, the average daily dose of donafenib is 522mg/day, treatment-related adverse events (TRAEs) are mostly grade 1-2, and overall compliance is good and safety is controllable
Thanks to the good results achieved by donafenib in the DIRECTION study, China's National Medical Products Administration (NMPA) approved donafenib for locally advanced/metastatic RAIR-DTC patients, which is expected to become a better choice
for the treatment of RAIR-DTC patients.
Guidelines for the diagnosis and treatment of thyroid cancer 2022 edition
Cong Hui,Liang Jun,Lin Yansong.
Diagnosis and targeted therapy of iodine-refractory differentiated thyroid cancer[J].
International Journal of Nuclear Medicine of Radiation Medicine,2015,39(01):25-31.
Shi, et al.
Donafenib in Locally Advanced/Metastatic, Radioactive Iodine-Refractory, Differentiated Thyroid Cancer: A Randomized, Double-blind, Placebo-controlled, Multi-Center Phase III Clinical Trial (DIRECTION).
ESMO Abstract 3099.