Real-world treatment outcomes and clinicopathologic and molecular determinants of response to first-line lenvatinib in patients with advanced follicular cell-derived thyroid cancer
Abstract 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...
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Nature Portfolio
2025-06-01
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| Online Access: | https://doi.org/10.1038/s44276-025-00153-2 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Kara M. Ruicci |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-7436eab719e94769b39c733bd380033d |
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| issn | 2731-9377 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | BJC Reports |
| spelling | doaj-art-7436eab719e94769b39c733bd380033d2025-08-20T02:05:49ZengNature PortfolioBJC Reports2731-93772025-06-01311810.1038/s44276-025-00153-2Real-world treatment outcomes and clinicopathologic and molecular determinants of response to first-line lenvatinib in patients with advanced follicular cell-derived thyroid cancerKara M. Ruicci0Yangqing Deng1Tian Xiao2Antoine Eskander3David Goldstein4Ozgur Mete5Aruz Mesci6Jelena Lukovic7Monika K. Krzyzanowska8Carly C. Barron9Lucy X. Ma10Radiation Medicine Program, Princess Margaret Cancer Centre, University Health NetworkDepartment of Biostatistics, University Health NetworkDivision of Medical Oncology, Department of Medicine, University of TorontoDepartment of Otolaryngology—Head & Neck Surgery, University of TorontoDepartment of Otolaryngology—Head & Neck Surgery, University of TorontoDepartment of Laboratory Medicine & Pathobiology, University of TorontoRadiation Medicine Program, Princess Margaret Cancer Centre, University Health NetworkRadiation Medicine Program, Princess Margaret Cancer Centre, University Health NetworkDivision of Medical Oncology, Department of Medicine, University of TorontoDivision of Medical Oncology, Department of Medicine, University of TorontoDivision of Medical Oncology, Department of Medicine, University of TorontoAbstract 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.https://doi.org/10.1038/s44276-025-00153-2 |
| spellingShingle | 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 Real-world treatment outcomes and clinicopathologic and molecular determinants of response to first-line lenvatinib in patients with advanced follicular cell-derived thyroid cancer BJC Reports |
| title | Real-world treatment outcomes and clinicopathologic and molecular determinants of response to first-line lenvatinib in patients with advanced follicular cell-derived thyroid cancer |
| title_full | Real-world treatment outcomes and clinicopathologic and molecular determinants of response to first-line lenvatinib in patients with advanced follicular cell-derived thyroid cancer |
| title_fullStr | Real-world treatment outcomes and clinicopathologic and molecular determinants of response to first-line lenvatinib in patients with advanced follicular cell-derived thyroid cancer |
| title_full_unstemmed | Real-world treatment outcomes and clinicopathologic and molecular determinants of response to first-line lenvatinib in patients with advanced follicular cell-derived thyroid cancer |
| title_short | Real-world treatment outcomes and clinicopathologic and molecular determinants of response to first-line lenvatinib in patients with advanced follicular cell-derived thyroid cancer |
| title_sort | real world treatment outcomes and clinicopathologic and molecular determinants of response to first line lenvatinib in patients with advanced follicular cell derived thyroid cancer |
| url | https://doi.org/10.1038/s44276-025-00153-2 |
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