Significance of BRAF V600E mutation in prediction of the efficacy of apatinib for radioactive iodine-refractory differentiated thyroid cancer / 中华核医学与分子影像杂志

ABSTRACT

Objective:To investigate the significance of B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation in the prediction of response to apatinib treatment in advanced radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC). Methods:Twenty patients (10 males, 10 females, age: 51.5(46.3, 65.0) years) with advanced RAIR-DTC from Peking Union Medical College Hospital between March 2016 and March 2023 were retrospectively enrolled, and all patients were treated with apatinib and underwent genetic sequencing (including BRAF V600E and telomerase reverse transcriptase (TERT) promoter). The serological and imaging data, progression-free survival (PFS) and overall survival (OS) data were collected during apatinib treatment. The Kaplan-Meier survival analysis (log-rank test) was performed, and Mann-Whitney U test were used to analyze the differences of duration of response (DOR) between mutation group and wild-type group. Then univariate and multivariate Cox regression analyses were conducted. Results:The PFS (35.3 vs 9.2 months, χ2=7.53, P=0.006) and DOR (25.8(7.4, 35.2) vs 8.2(2.5, 13.4) months, U=23.00, P=0.046) of the BRAF V600E mutation group were longer than those of the wild-type group. Univariate Cox regression analysis showed that the BRAF V600E mutation group had better PFS benefit (hazard ratio ( HR)=0.22 (95% CI: 0.06-0.72), P=0.013), and the risk of disease progression or death in patients with lung metastasis and bone or brain metastasis was 3.06(95% CI: 1.10-8.54, P=0.033) times higher than that in patients with lung metastasis alone. Further, multivariate cox regression analysis showed that only BRAF V600E mutation was an independent predictor of PFS ( HR=0.23 (95% CI: 0.07-0.80), P=0.021), suggesting that RAIR-DTC patients with BRAF V600E mutation might have better efficacy of apatinib. There was no significant difference in PFS ( χ2=1.34, P=0.247) and OS ( χ2=0.19, P=0.664) between TERT promoter mutation group and wild-type group. Conclusion:RAIR-DTC patients with BRAF V600E mutation have longer PFS and DOR after apatinib treatment than those with BRAF V600E wild-type, suggesting that BRAF V600E may be a potential biomarker to guide tyrosine kinase inhibitor (TKI) therapy and help to refine TKI treatment indications.