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Background <p>The antiangiogenic multi-kinase inhibitors (MKIs) apatinib, donafenib, and anlotinib have demonstrated satisfactory efficacy in radioactive iodine refractory differentiated thyroid cancer (RAIR-DTC) in their phase II/III trials. However, the potential impact factors on the efficacy of these MKIs remain unclear.</p> Methods <p>RAIR-DTC patients enrolled in clinical trials of apatinib, donafenib, and anlotinib in our center were retrospectively reviewed. The Kaplan–Meier method was used to examine the relationship between clinicopathological variables and progression-free survival (PFS) and overall survival (OS), followed by a multivariate Cox analysis on PFS.</p> Results <p>A total of 71 progressive RAIR-DTC patients were reviewed, of which 26.7% were treated by anlotinib, 45.1% by apatinib, and 28.2% by donafenib. The median follow-up time was 44.1&#xa0;months, the median PFS was 21.1&#xa0;months, and the estimated median OS was 47.7&#xa0;months. PFS and OS showed no significant differences in patients treated with apatinib, donafenib, or anlotinib. In the univariate analyses, patients with <i>BRAF</i><sup><i>V600E</i></sup> mutation showed longer PFS (HR 0.345, 95% CI 0.187–0.636, <i>p</i> &lt; 0.001) and OS (HR 0.382, 95% CI 0.166–0.878, <i>p</i> = 0.019) compared with patients with wild-type <i>BRAF</i>. Patients with follicular thyroid cancer and bone metastases had shorter PFS, and patients with worse Eastern Cooperative Oncology Group performance status, bone metastases, and a larger tumor burden had shorter OS. In the multivariate Cox analysis, <i>BRAF</i><sup><i>V600E</i></sup> mutation was the only independent predictor of longer PFS (HR 0.296, 95% CI 0.138–0.638, <i>p</i> = 0.002). The overall response rate and disease control rate didn’t differ between <i>BRAF</i><sup><i>V600E</i></sup> mutation status. Subgroup analysis of PFS in papillary thyroid cancer patients stratified by <i>BRAF</i><sup><i>V600E</i></sup> mutation status showed that <i>BRAF</i><sup><i>V600E</i></sup> mutation was associated with longer PFS in all clinicopathological subgroups (hazard ratio &lt; 1).</p> Conclusion <p>RAIR-DTC patients with <i>BRAF</i><sup><i>V600E</i></sup> mutation treated with apatinib, donafenib, or anlotinib achieved better prognoses compared with patients with wild-type <i>BRAF</i>, indicating that the genetic background may play a role in predicting the efficacy of MKIs therapies.</p> Trial registration <p>This retrospective cohort included patients in our center from clinical trials of apatinib (NCT02731352, NCT03048877), donafenib (NCT02870569, NCT03602495), and anlotinib (NCT05007093).</p>

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BRAFV600E mutation is associated with better prognoses in radioactive iodine refractory thyroid cancer patients treated with multi-kinase inhibitors: a retrospective analysis of registered clinical trials

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  • 发表日期：

    2025年2月10日

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  • Di Sun,
  • Xin Zhang,
  • Xiaona Jin,
  • Cong Shi,
  • Yuqing Sun,
  • Yingqiang Zhang,
  • Jun Liang,
  • Yansong Lin

摘要

Background

The antiangiogenic multi-kinase inhibitors (MKIs) apatinib, donafenib, and anlotinib have demonstrated satisfactory efficacy in radioactive iodine refractory differentiated thyroid cancer (RAIR-DTC) in their phase II/III trials. However, the potential impact factors on the efficacy of these MKIs remain unclear.

Methods

RAIR-DTC patients enrolled in clinical trials of apatinib, donafenib, and anlotinib in our center were retrospectively reviewed. The Kaplan–Meier method was used to examine the relationship between clinicopathological variables and progression-free survival (PFS) and overall survival (OS), followed by a multivariate Cox analysis on PFS.

Results

A total of 71 progressive RAIR-DTC patients were reviewed, of which 26.7% were treated by anlotinib, 45.1% by apatinib, and 28.2% by donafenib. The median follow-up time was 44.1 months, the median PFS was 21.1 months, and the estimated median OS was 47.7 months. PFS and OS showed no significant differences in patients treated with apatinib, donafenib, or anlotinib. In the univariate analyses, patients with BRAFV600E mutation showed longer PFS (HR 0.345, 95% CI 0.187–0.636, p < 0.001) and OS (HR 0.382, 95% CI 0.166–0.878, p = 0.019) compared with patients with wild-type BRAF. Patients with follicular thyroid cancer and bone metastases had shorter PFS, and patients with worse Eastern Cooperative Oncology Group performance status, bone metastases, and a larger tumor burden had shorter OS. In the multivariate Cox analysis, BRAFV600E mutation was the only independent predictor of longer PFS (HR 0.296, 95% CI 0.138–0.638, p = 0.002). The overall response rate and disease control rate didn’t differ between BRAFV600E mutation status. Subgroup analysis of PFS in papillary thyroid cancer patients stratified by BRAFV600E mutation status showed that BRAFV600E mutation was associated with longer PFS in all clinicopathological subgroups (hazard ratio < 1).

Conclusion

RAIR-DTC patients with BRAFV600E mutation treated with apatinib, donafenib, or anlotinib achieved better prognoses compared with patients with wild-type BRAF, indicating that the genetic background may play a role in predicting the efficacy of MKIs therapies.

Trial registration

This retrospective cohort included patients in our center from clinical trials of apatinib (NCT02731352, NCT03048877), donafenib (NCT02870569, NCT03602495), and anlotinib (NCT05007093).