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Background <p>There is a paucity of real-world data regarding lenvatinib for locally-recurrent, metastatic and RAI-refractory thyroid cancer. Here we examined the efficacy of first-line lenvatinib in a genomically-characterized cohort and identified clinicopathological/molecular correlates of drug response.</p> Methods <p>Patients with advanced follicular cell-derived thyroid cancer who underwent NGS at Princess Margaret Cancer Centre and commenced first-line lenvatinib monotherapy between 2015-2023 were included. Kaplan-Meier method, log-rank tests and univariable/multivariable proportional hazard models were employed.</p> Results <p>In total, 77 patients were included (48% female, majority papillary (52%), poorly differentiated (17%) or invasive encapsulated follicular variant papillary (16%)). Most (79%) underwent total thyroidectomy and adjuvant RAI (median cumulative dose 231 mCi). At lenvatinib initiation, median age was 62.9 years, 68% were ECOG performance status ≥2, 81% had lung metastases, 53% had bone metastases and 8% had liver metastases. Most patients started with <Emphasis FontCategory="NonProportional">≤</Emphasis>14 mg of lenvatinib daily. Median time to treatment discontinuation was 33 months. Older age, ECOG ≥ 2, liver metastases and <i>TP53</i> mutation(s) were associated with shorter time to treatment discontinuation; ECOG ≥ 2 and <i>TP53</i> mutation(s) remained significant on multivariable analysis.</p> Conclusion <p>Our findings reinforce the clinical efficacy of lenvatinib in advanced thyroid cancer patients with heterogenous clinicopathologic/molecular features and highlight variables for future treatment stratification.</p>

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Real-world treatment outcomes and clinicopathologic and molecular determinants of response to first-line lenvatinib in patients with advanced follicular cell-derived thyroid cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月3日

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  • Kara M. Ruicci,
  • Yangqing Deng,
  • Tian Xiao,
  • Antoine Eskander,
  • David Goldstein,
  • Ozgur Mete,
  • Aruz Mesci,
  • Jelena Lukovic,
  • Monika K. Krzyzanowska,
  • Carly C. Barron,
  • Lucy X. Ma

摘要

Background

There is a paucity of real-world data regarding lenvatinib for locally-recurrent, metastatic and RAI-refractory thyroid cancer. Here we examined the efficacy of first-line lenvatinib in a genomically-characterized cohort and identified clinicopathological/molecular correlates of drug response.

Methods

Patients with advanced follicular cell-derived thyroid cancer who underwent NGS at Princess Margaret Cancer Centre and commenced first-line lenvatinib monotherapy between 2015-2023 were included. Kaplan-Meier method, log-rank tests and univariable/multivariable proportional hazard models were employed.

Results

In total, 77 patients were included (48% female, majority papillary (52%), poorly differentiated (17%) or invasive encapsulated follicular variant papillary (16%)). Most (79%) underwent total thyroidectomy and adjuvant RAI (median cumulative dose 231 mCi). At lenvatinib initiation, median age was 62.9 years, 68% were ECOG performance status ≥2, 81% had lung metastases, 53% had bone metastases and 8% had liver metastases. Most patients started with ≤14 mg of lenvatinib daily. Median time to treatment discontinuation was 33 months. Older age, ECOG ≥ 2, liver metastases and TP53 mutation(s) were associated with shorter time to treatment discontinuation; ECOG ≥ 2 and TP53 mutation(s) remained significant on multivariable analysis.

Conclusion

Our findings reinforce the clinical efficacy of lenvatinib in advanced thyroid cancer patients with heterogenous clinicopathologic/molecular features and highlight variables for future treatment stratification.