Antitumour effects of apatinib in progressive, metastatic differentiated thyroid cancer (DTC)

Liang Shi, Qinqin You, Jun Wang, Hanjin Wang, Shaohua Li, Rui Tian, Xiaocheng Yao, Wenyu Wu, Lele Zhang, Feng Wang, Yansong Lin, Shuren Li, Liang Shi, Qinqin You, Jun Wang, Hanjin Wang, Shaohua Li, Rui Tian, Xiaocheng Yao, Wenyu Wu, Lele Zhang, Feng Wang, Yansong Lin, Shuren Li

Abstract

Purpose: Management of progressive, metastatic radioactive iodine refractory differentiated thyroid cancer (RAIR-DTC) has been a great challenge due to its poor prognosis and limited treatment options. Recently, apatinib, an orally anti-angiogenic tyrosine kinase inhibitor (TKI) is reported to be useful for treatment of progressive RAIR-DIC. The aim of this study was to evaluate the antitumour effect of apatinib and the combination therapy with radioactive iodine (RAI) in patients with progressive metastatic DTC.

Methods: Five patients (all female, mean age 62 ± 8 years, ranged from 51 to 69 years) with distant metastatic DTC (dmDTC) after total thyroidectomy (TTE) and neck lymph node dissection were treated with apatinib at a dose 500 mg per day after 18F-Fluorodeoxyglucose (18F-FDG) PET/CT. The effects of apatinib on DTC were evaluated at 4 ± 1 months after treatment with apatinib. RAI therapy was then initiated. The response to apatinib and the combination therapy with RAI treatment was evaluated by Response Evaluation Criteria in Solid Tumours (RECIST, version 1.1) and metabolic activity using serum thyroglobulin (Tg) and 18F-FDG PET/CT.

Results: Positive 18F-FDG PET/CT results were found in all patients before apatinib therapy. The immunohistochemical analysis of primary tumour tissues showed high expression of vascular endothelial growth factor receptor-2 (VEGFR-2). Four patients with follicular thyroid carcinoma (FTC) showed partial response (PR) with significant decrease in tumour size and maximum standardized uptake value (SUVmax) after 4 ± 1 month's treatment with apatinib. Further significant reduction of tumour size and SUVmax were observed in three patients after combination therapy with apatinib and RAI. Only one patient with both FTC and papillary thyroid cancer (PTC) demonstrated progressive disease (PD) after treatment with apatinib alone, however, a decrease in tumour size and SUVmax as well as serum Tg levels was achieved after the combination with RAI therapy and apatinib.

Conclusions: Apatinib had significant antitumour effects on progressive distant metastatic DTC. Moreover, beneficial synergistic and complementary effects were shown when apatinib combined with RAI therapy.

Clinical trial registration: NCT04180007, Registered November 26, 2019.

Keywords: Apatinib; Metastatic differentiated thyroid cancer; Radioactive iodine (RAI); Tyrosine kinase inhibitor.

Conflict of interest statement

The author declares no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Patient flow diagram
Fig. 2
Fig. 2
In case 1, 18F-FDG PET/CT showed dmDTC before apatinib therapy (A, Aa, Ab, Ca and Cb). Decreased tumour sizes and SUVmax in the right 10th rib (red arrows) and in the left acetabulum (orange arrows) after neoadjuvant therapy with apatinib for 4 months (B, Ba, Bb, Da and Db) and further decrease in tumour size in the left acetabulum after apatinib combined with RAI (Ea and Eb). Immunohistochemistry assay confirmed expression of VEGFR2 in the tumour tissue (Magnification, ×400) (F). The post-therapeutic 131I whole-body scans in anterior and posterior views were shown (G)
Fig. 3
Fig. 3
The post-therapeutic 131I whole-body scans of patient (No. 2 in Table 1) in anterior and posterior views (A) as well as CT (B) and SPECT/CT (C) of pelvic bone were shown. Red arrows indicated metastases. A post-therapeutic 131I whole-body scans of another patient (No. 3 in Table 1) in anterior and posterior views (D) were demonstrated. Orange arrows indicated metastases
Fig. 4
Fig. 4
In case 4, 18F-FDG PET/CT revealed multiple mediastinal lymph nodes, pulmonary, liver and left 5th to 9th ribs as well as left thoracic wall metastases (A, Aa and Ab). Decreased tumour size and SUVmax after 4-month therapy with apatinib (B, Ba and Bb). However, no further decrease of tumour size was observed after apatinib therapy combined with RAI (C, Ca and Cb). Red arrows indicated metastases in left 5th to 9th ribs as well as left thoracic wall. The negative post-therapeutic 131I whole body scans in anterior and posterior views (D) and CT (Da) as well as SPECT/CT (Db) of liver metastasis were shown. The black arrows in D indicated thyroid remnant
Fig. 5
Fig. 5
In case 5, 18F-FDG PET/CT showed bone (right 5th rib and right acetabulum) metastases before apatinib therapy (A and Aa to Ad). Increased tumour sizes and a new metastasis formation in the right ilium were revealed after 6-month therapy with apatinib (B, Ba to Bd). After combined therapy with RAI, decreases in tumour sizes and SUVmax were shown (C, Ca to Cd). The post-therapeutic 131I whole body scans in anterior and posterior views (D) and CT (Da) as well as SPECT/CT (Db) of 5th rib metastases were shown. Red arrows indicated metastasis in the right 5th rib and orange arrows metastases in the right acetabulum

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Source: PubMed

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