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

George W. Sledge (), Takayuki Yoshino, Joanne Xiu, Anthony Helmstetter, Jennifer R. Ribeiro, Sergey Klimov, Brady Gilg, Gao Jj, Jeff Elton, Matthew J. Oberley, Milan Radovich, Jim Abraham and David Spetzler
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George W. Sledge: 4610 S 44th Pl
Takayuki Yoshino: 〒277-8577 Chiba
Joanne Xiu: 4610 S 44th Pl
Anthony Helmstetter: 4610 S 44th Pl
Jennifer R. Ribeiro: 4610 S 44th Pl
Sergey Klimov: 4610 S 44th Pl
Brady Gilg: 4610 S 44th Pl
Gao Jj: 4610 S 44th Pl
Jeff Elton: 1120 Massachusetts Ave
Matthew J. Oberley: 4610 S 44th Pl
Milan Radovich: 4610 S 44th Pl
Jim Abraham: 4610 S 44th Pl
David Spetzler: 4610 S 44th Pl

Nature Communications, 2025, vol. 16, issue 1, 1-11

Abstract: Abstract 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.

Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57941-0

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DOI: 10.1038/s41467-025-57941-0

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