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<p>The US Food and Drug Administration approves tissue-agnostic therapies to target tumor biomarkers regardless of tumor type. In light of the growing number of such approvals in recent years, a better understanding of their relative clinical benefit across cancer types is required. To address this need, we analyzed tissue-agnostic indications (TMB-High, MSI-High/MMRd, <i>BRAF</i><sup>V600E</sup> mutations, and <i>NTRK</i> and <i>RET</i> fusions) in a database of 295,316 molecularly-profiled tumor samples with associated clinical outcomes data. Here, we show that 21.5% of tumors harbored at least one of the tissue-agnostic indications investigated, including 5.4% lacking a cancer-specific indication. Our analysis reveals poor uptake of targeted therapies for rare <i>NTRK</i> fusions, significant differences in pembrolizumab-associated outcomes across tumor types for TMB-High and MSI-High/MMRd, as well as clinical benefits in tumor types and drugs of the same class not investigated in the pivotal clinical trials. These results demonstrate that treatment effects are not necessarily tissue-agnostic, and suggest possible expansion of therapeutic avenues for a given tissue-agnostic indication.</p>

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Real-world evidence provides clinical insights into tissue-agnostic therapeutic approvals

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年3月18日

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  • George W. Sledge Jr.,
  • Takayuki Yoshino,
  • Joanne Xiu,
  • Anthony Helmstetter,
  • Jennifer R. Ribeiro,
  • Sergey Klimov,
  • Brady Gilg,
  • JJ Gao,
  • Jeff Elton,
  • Matthew J. Oberley,
  • Milan Radovich,
  • Jim Abraham,
  • David Spetzler

摘要

The US Food and Drug Administration approves tissue-agnostic therapies to target tumor biomarkers regardless of tumor type. In light of the growing number of such approvals in recent years, a better understanding of their relative clinical benefit across cancer types is required. To address this need, we analyzed tissue-agnostic indications (TMB-High, MSI-High/MMRd, BRAFV600E mutations, and NTRK and RET fusions) in a database of 295,316 molecularly-profiled tumor samples with associated clinical outcomes data. Here, we show that 21.5% of tumors harbored at least one of the tissue-agnostic indications investigated, including 5.4% lacking a cancer-specific indication. Our analysis reveals poor uptake of targeted therapies for rare NTRK fusions, significant differences in pembrolizumab-associated outcomes across tumor types for TMB-High and MSI-High/MMRd, as well as clinical benefits in tumor types and drugs of the same class not investigated in the pivotal clinical trials. These results demonstrate that treatment effects are not necessarily tissue-agnostic, and suggest possible expansion of therapeutic avenues for a given tissue-agnostic indication.