4.7 Article

A computational method for prioritizing targeted therapies in precision oncology: performance analysis in the SHIVA01 trial

Journal

NPJ PRECISION ONCOLOGY
Volume 5, Issue 1, Pages -

Publisher

NATURE RESEARCH
DOI: 10.1038/s41698-021-00191-2

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Funding

  1. Agence Nationale de le Recherche
  2. Site de Recherche Integree contre le Cancer (SiRIC) (ERA PerMed) [ERAPERMED2018-078]
  3. Hungarian Innovation Agency [NVKP_16-1-2016-0005, 2019-1.1.1-PIACI-KFI-2019-00367, TUDFO/51757/2019-ITM, TKP 2020-NKA-19]

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The study introduces an artificial intelligence-assisted computational method, the digital drug-assignment (DDA) system, to prioritize potential molecularly targeted agents (MTAs) for each cancer patient based on their individual molecular profile. Results from the clinical trial show that patients with higher DDA scores experienced better disease control and longer progression-free survival compared to those with lower scores, indicating promising potential of AI-based systems like DDA in improving precision oncology outcomes.
Precision oncology is currently based on pairing molecularly targeted agents (MTA) to predefined single driver genes or biomarkers. Each tumor harbors a combination of a large number of potential genetic alterations of multiple driver genes in a complex system that limits the potential of this approach. We have developed an artificial intelligence (AI)-assisted computational method, the digital drug-assignment (DDA) system, to prioritize potential MTAs for each cancer patient based on the complex individual molecular profile of their tumor. We analyzed the clinical benefit of the DDA system on the molecular and clinical outcome data of patients treated in the SHIVA01 precision oncology clinical trial with MTAs matched to individual genetic alterations or biomarkers of their tumor. We found that the DDA score assigned to MTAs was significantly higher in patients experiencing disease control than in patients with progressive disease (1523 versus 580, P = 0.037). The median PFS was also significantly longer in patients receiving MTAs with high (1000+ <) than with low (<0) DDA scores (3.95 versus 1.95 months, P = 0.044). Our results indicate that AI-based systems, like DDA, are promising new tools for oncologists to improve the clinical benefit of precision oncology.

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