Antitumour effects of apatinib in progressive, metastatic differentiated thyroid cancer (DTC)
Liang Shi1, Qinqin You1, Jun Wang1
1Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
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.
Insights
Apatinib shows significant anti-tumor effects in patients with progressive metastatic differentiated thyroid cancer (DTC). Combining apatinib with radioactive iodine (RAI) therapy demonstrates synergistic benefits for treating advanced DTC.
Area of Science:
- Oncology
- Radiopharmaceuticals
- Pharmacology
Background:
- Differentiated thyroid cancer (DTC) that is metastatic and refractory to radioactive iodine (RAIR-DTC) presents a significant clinical challenge due to limited treatment options and poor prognosis.
- Apatinib, an oral anti-angiogenic tyrosine kinase inhibitor (TKI), has emerged as a potential therapeutic agent for progressive RAIR-DTC.
Purpose of the Study:
- To evaluate the anti-tumor efficacy of apatinib as a monotherapy and in combination with radioactive iodine (RAI) for patients with progressive metastatic DTC.
- To assess the impact of apatinib and combination therapy on tumor size, metabolic activity, and serum thyroglobulin levels.
Main Methods:
- A study involving five female patients with distant metastatic DTC (dmDTC) who received apatinib (500 mg/day) post-thyroidectomy and lymph node dissection, monitored by 18F-FDG PET/CT.
- Evaluation of treatment response using Response Evaluation Criteria in Solid Tumors (RECIST v1.1), serum thyroglobulin (Tg), and 18F-FDG PET/CT before and after apatinib therapy, followed by RAI treatment.
Main Results:
- All patients exhibited positive 18F-FDG PET/CT results and high VEGFR-2 expression in tumor tissues prior to apatinib treatment.
- Four out of five patients with follicular thyroid carcinoma (FTC) achieved partial response (PR) with apatinib alone, showing reduced tumor size and SUVmax.
- Combination therapy with apatinib and RAI led to further significant reductions in tumor size and SUVmax in three patients, and improved outcomes in the one patient with progressive disease on apatinib monotherapy.
Conclusions:
- Apatinib demonstrates significant anti-tumor activity in progressive metastatic DTC.
- The combination of apatinib with RAI therapy exhibits beneficial synergistic and complementary effects, improving treatment outcomes for advanced DTC.
