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Agnostic Approvals in Oncology: Getting the Right Drug to the Right Patient with the Right Genomics
Valentina Tateo1, Paola Valeria Marchese1, Veronica Mollica1
1Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.
Abstract:
(1) Background: The oncology field has drastically changed with the advent of precision medicine, led by the discovery of druggable genes or immune targets assessed through next-generation sequencing. Biomarker-based treatments are increasingly emerging, and currently, six tissue-agnostic therapies are FDA-approved. (2) Methods: We performed a review of the literature and reported the trials that led to the approval of tissue-agnostic treatments and ongoing clinical trials currently investigating novel biomarker-based approaches. (3) Results: We discussed the approval of agnostic treatments: pembrolizumab and dostarlimab for MMRd/MSI-H, pembrolizumab for TMB-H, larotrectinib and entrectinib for NTRK-fusions, dabrafenib plus trametinib for BRAF V600E mutation, and selpercatinib for RET fusions. In addition, we reported novel clinical trials of biomarker-based approaches, including ALK, HER2, FGFR, and NRG1. (4) Conclusions: Precision medicine is constantly evolving, and with the improvement of diagnostic tools that allow a wider genomic definition of the tumor, tissue-agnostic targeted therapies are a promising treatment strategy tailored to the specific tumor genomic profile, leading to improved survival outcomes.
Insights
Precision medicine in oncology offers targeted therapies based on specific genetic biomarkers, not tumor location. Six FDA-approved tissue-agnostic treatments demonstrate this approach
Area of Science:
- Oncology
- Genomics
- Precision Medicine
Background:
- The oncology landscape has been transformed by precision medicine, driven by next-generation sequencing to identify druggable genes and immune targets.
- Biomarker-driven therapies are increasingly prevalent, with six FDA-approved tissue-agnostic treatments currently available.
Purpose of the Study:
- To review the literature on pivotal clinical trials leading to the approval of tissue-agnostic cancer treatments.
- To report on ongoing clinical trials exploring novel biomarker-based therapeutic strategies.
Main Methods:
- Comprehensive literature review of clinical trials.
- Analysis of FDA-approved tissue-agnostic therapies and their associated biomarkers.
- Identification and summary of current clinical trials investigating new biomarker-based approaches.
Main Results:
- Discussion of approved agnostic treatments: pembrolizumab and dostarlimab (MMRd/MSI-H), pembrolizumab (TMB-H), larotrectinib and entrectinib (NTRK-fusions), dabrafenib plus trametinib (BRAF V600E), and selpercatinib (RET fusions).
- Overview of ongoing trials for novel biomarkers including ALK, HER2, FGFR, and NRG1.
Conclusions:
- Precision medicine is rapidly advancing, with improved diagnostic tools enabling broader genomic tumor profiling.
- Tissue-agnostic targeted therapies represent a promising strategy, personalizing treatment to individual tumor genomic profiles.
- This approach holds potential for significantly improved patient survival outcomes.
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