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<p>Tissue-agnostic therapies, which target molecular alterations across cancer types, have been approved by the US Food and Drug Administration (FDA) since 2017. These approvals were based on clinical trials enrolling patients across diverse tumor types, regardless of the tumor’s site of origin. This analysis evaluated the efficacy and safety of FDA-approved tissue-agnostic therapies in patients with lung cancer, the leading cause of cancer-related deaths worldwide, harboring targetable genetic alterations. Current evidence suggests that these therapies show promise in treating <i>NTRK</i> gene fusions (larotrectinib, entrectinib, repotrectinib), <i>BRAF</i> V600E mutation (dabrafenib and trametinib), and <i>RET</i> fusions (selpercatinib) in lung cancer. Reported rates of grade 3 or higher treatment-related or treatment-emergent adverse events ranged from 10 to 59.7%. However, available data are limited by small sample sizes (ranging from 4 to 247 participants per trial-cohort) and the absence of control groups. Larger, controlled studies and real-world evaluations are needed to confirm these findings and inform broader clinical use.</p>

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The Utility of Tissue-Agnostic Drugs in Lung Cancer Treatment

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月1日

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  • Leping Kong,
  • Ben Grobman,
  • Arian Mansur,
  • Adele Lee,
  • Connor Bondarchuk,
  • Hannah Erdogan,
  • Christine Y. Lu

摘要

Tissue-agnostic therapies, which target molecular alterations across cancer types, have been approved by the US Food and Drug Administration (FDA) since 2017. These approvals were based on clinical trials enrolling patients across diverse tumor types, regardless of the tumor’s site of origin. This analysis evaluated the efficacy and safety of FDA-approved tissue-agnostic therapies in patients with lung cancer, the leading cause of cancer-related deaths worldwide, harboring targetable genetic alterations. Current evidence suggests that these therapies show promise in treating NTRK gene fusions (larotrectinib, entrectinib, repotrectinib), BRAF V600E mutation (dabrafenib and trametinib), and RET fusions (selpercatinib) in lung cancer. Reported rates of grade 3 or higher treatment-related or treatment-emergent adverse events ranged from 10 to 59.7%. However, available data are limited by small sample sizes (ranging from 4 to 247 participants per trial-cohort) and the absence of control groups. Larger, controlled studies and real-world evaluations are needed to confirm these findings and inform broader clinical use.