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<p>Background Lenvatinib is a standard first-line therapy for radioiodine-refractory papillary thyroid carcinoma (PTC). However, the influence of genomic alterations on its efficacy remains unclear. Methods We conducted a nationwide, retrospective study using the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database in Japan, analyzing 165 patients with PTC who received lenvatinib as first-line treatment. Time to treatment failure (TTF) was compared based on <i>BRAF</i> and telomerase reverse transcriptase (<i>TERT</i>) promoter mutations and other recurrent genomic alterations. Kaplan–Meier and Cox models were used. Results <i>BRAF</i> mutations were present in 79% of patients and <i>TERT</i> mutations in 72%. <i>BRAF</i> mutation was associated with longer TTF (adjusted hazard ratio [HR]: 0.62, <i>p</i> = 0.07). <i>TERT</i> mutation alone or in combination with <i>BRAF</i> mutation did not affect TTF. Mutations in five genes, <i>KMT2A</i>, <i>MTOR</i>, <i>MUTYH</i>, <i>CREBBP</i>, and <i>RICTOR</i>, were independently associated with shorter TTF (adjusted HRs 2.04–2.80). These results were supported by variant-level review but did not retain significance after false-discovery-rate adjustment, indicating their exploratory nature. Conclusions Lenvatinib showed substantial efficacy in <i>BRAF</i>-mutated PTC, while <i>TERT</i> mutations did not predict poor outcomes. The identification of five genes associated with early treatment failure highlights the potential for genomic biomarkers to guide personalized therapy.</p>

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Impact of BRAF, TERT, and novel mutations on the efficacy of lenvatinib for advanced papillary thyroid cancer: A national genomic database analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月18日

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  • Yasuyoshi Sato,
  • Naoki Fukuda,
  • Koji Yamamura,
  • Yusuke Ito,
  • Kenya Kobayashi,
  • Yuki Saito,
  • Kousuke Watanabe,
  • Hidenori Kage,
  • Katsutoshi Oda,
  • Shunji Takahashi

摘要

Background Lenvatinib is a standard first-line therapy for radioiodine-refractory papillary thyroid carcinoma (PTC). However, the influence of genomic alterations on its efficacy remains unclear. Methods We conducted a nationwide, retrospective study using the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database in Japan, analyzing 165 patients with PTC who received lenvatinib as first-line treatment. Time to treatment failure (TTF) was compared based on BRAF and telomerase reverse transcriptase (TERT) promoter mutations and other recurrent genomic alterations. Kaplan–Meier and Cox models were used. Results BRAF mutations were present in 79% of patients and TERT mutations in 72%. BRAF mutation was associated with longer TTF (adjusted hazard ratio [HR]: 0.62, p = 0.07). TERT mutation alone or in combination with BRAF mutation did not affect TTF. Mutations in five genes, KMT2A, MTOR, MUTYH, CREBBP, and RICTOR, were independently associated with shorter TTF (adjusted HRs 2.04–2.80). These results were supported by variant-level review but did not retain significance after false-discovery-rate adjustment, indicating their exploratory nature. Conclusions Lenvatinib showed substantial efficacy in BRAF-mutated PTC, while TERT mutations did not predict poor outcomes. The identification of five genes associated with early treatment failure highlights the potential for genomic biomarkers to guide personalized therapy.