Prospective study of the real impact of fusion centered genomic assays in patient management in a national collaborative group: the GETHI-XX-16 study

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发表日期：

2024年11月1日

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Paloma Navarro,
Carmen Beato,
Juan Francisco Rodriguez-Moreno,
Sergio Ruiz-Llorente,
Xabier Mielgo,
Estela Pineda,
Miguel Navarro,
Gema Bruixola,
Tatiana P. Grazioso,
Antonio Viudez,
Jose Fuster,
Esther Nogueron,
Maria Dolores Mediano,
Carmen Balaña,
Carlos Mendez,
Rosa María Rodriguez,
Sonia del Barco Berron,
Beatriz Gongora,
Alberto Carmona-Bayonas,
Jesus Garcia-Donas

摘要

Purpose

Precision medicine represents a paradigm shift in oncology. Access to genetic testing and targeted therapies is frequently limited. Assays based on DNA sequencing can miss druggable alterations. We aimed to determine the impact of a free access program to RNA tests in patient management.

Methods

We designed a multicenter prospective observational study within the Spanish National Group for Translational Oncology and Rare and Orphan Tumors (GETTHI). Eligible patients were adults with solid cancers that had progressed on standard therapies. Tumor samples were analyzed using two RNA sequencing assays (Trailblaze Pharos^TM and Archer FusionPlex Solid Tumor^TM). A central committee evaluated the actionability of genetic alterations and reported the findings to attending physicians, who made the final clinical management decisions.

Results

Between November 2016 and April 2019, 395 patients with 41 different tumors across 30 hospitals were included. Molecular analysis revealed actionable genetic alterations in 57 individuals (14.4%). Targeted therapies were advised for 23 and seven received a matched targeted therapy: two lung cancers (EML4-ALK and CD74-ROS1 fusion), three glioblastomas (EGFR point mutations), one oligodendroglioma (FGFR3-TACC3 fusion) and a prostate cancer (SND1-BRAF fusion). The outcomes included two tumor responses, one disease stabilization, one early withdrawal due to toxicity, one progression, and one unknown.

Conclusion

Despite the growing knowledge of cancer biology and its translation to drug development, the overall impact of personalized treatments remains low. Access to comprehensive molecular tests covering properly all known actionable alterations and programs for a wide access to targeted therapies seem to be critical steps.