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Review
. 2023 Mar;9(3):237-249.
doi: 10.1016/j.trecan.2022.11.003. Epub 2022 Dec 7.

Impact of tissue-agnostic approvals for patients with gastrointestinal malignancies

Deepak Bhamidipati  1 , Vivek Subbiah  2
Affiliations
Review

Impact of tissue-agnostic approvals for patients with gastrointestinal malignancies

Deepak Bhamidipati et al. Trends Cancer. 2023 Mar.

Abstract

Gastrointestinal (GI) malignancies encompass a broad range of tumors with limited treatment options, particularly for advanced disease. With the development and implementation of next-generation sequencing (NGS) in routine practice, molecular-targeting therapies have been increasingly incorporated into the treatment paradigm for various cancers. Several drugs have achieved tissue-agnostic regulatory approvals, which offer promising biomarker-driven therapy options for patients with advanced GI malignancies. In this review, we focus on the clinical evidence for recent drug approvals for neurotrophic tyrosine receptor kinase (NTRK) fusion, microsatellite instability-high (MSI-H) phenotype, tumor mutation burden-high (TMB-H), BRAF V600E, and rearranged during transfection (RET), in the context of GI malignancies. We also highlight the future landscape of tissue-agnostic targets, such as human epidermal growth factor receptor 2 (HER2)/neu, fibroblast growth factor receptor (FGFR), and neuregulin (NRG)-1.

Keywords: cancer clinical trials; next-generation sequencing; targeted therapy; tissue-agnostic.

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Conflict of interest statement

Declaration of interests V.S. reports research funding/grant support for clinical trials from AbbVie, Agensys, Inc., Alfasigma, Altum, Amgen, Bayer, BERG Health, Blueprint Medicines Corporation, Boston Biomedical, Inc., Boston Pharmaceuticals, Celgene Corporation, D3 Bio, Inc., Dragonfly Therapeutics, Inc., Exelixis, Fujifilm, GlaxoSmithKline, Idera Pharmaceuticals, Inc., Incyte Corporation, Inhibrx, Loxo Oncology, MedImmune, MultiVir, Inc., NanoCarrier, Co., National Comprehensive Cancer Network, NCI-CTEP, Northwest Biotherapeutics, Novartis, PharmaMar, Pfizer, Relay Therapeutics, Roche/Genentech, Takeda, Turning Point Therapeutics, UT MD Anderson Cancer Center, and Vegenics Pty Ltd.; travel support from ASCO, ESMO, Helsinn Healthcare, Incyte Corporation, Novartis, and PharmaMar; consultancy/advisory board participation for Helsinn Healthcare, Jazz Pharmaceuticals, Incyte Corporation, Loxo Oncology/Eli Lilly, MedImmune, Novartis, QED Therapeutics, Relay Therapeutics, Daiichi-Sankyo, and R-Pharm US; and an additional relationship with Medscape. D.B. reports no conflicts of interest.

Figures

Figure 1. Key Figure.
Figure 1. Key Figure.. Current and future tissue agnostic therapies in GI malignancies.
Various drugs have been approved or are in development for tissue-agnostic approvals which are relevant to patients with gastrointestinal malignancies. Enterectenib and Larotrectinib have tissue agnostic approvals to target neurotrophic tyrosine receptor kinase (NTRK) fusions. Pembrolizumab and dostarlimab-glxy have tissue agnostic approvals to target deficient mismatch repair (dMMR)/microsatellite instability high (MSI-H) cancers while pembrolizumab also has a tissue agnostic indication for tumors with high tumor mutational burden (TMB). Selpercatinib and Pralsetinib have tissue agnostic indications for RET fusion positive cancers and Vemurafenib/Dabrafenib for cancers with BRAF V600E mutation. Alofanib, pemigatinib, and bemarituzumab have promising tissue agnostic activity in gastrointestinal tumors with fibroblast growth factor receptors (FGFR) fusions and Zenocotuzumab is a promising agent with activity in Neuregulin 1 (NRG1) fusion positive cancers. Human Epidermal Growth Factor Receptor 2 (HER2) targeted agents have several FDA approvals for gastrointestinal malignancies.
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References

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