Tumor-Agnostic Treatment for Cancer: When How is Better than Where

AbstractIn the evolving landscape of precision oncology, genomic characterization of tumor has become crucial in order to move toward a molecular-based therapy for the vast majority of cancers. Recently, translational research has offered new perspectives in systemic cancer treatment thanks to the identification of novel oncogenic targets and the development of new targeted therapies, followed by the latest applications of genomic sequencing. Simultaneously, next-generation sequencing (NGS) has expanded its accessibility, being incorporated into clinical studies at the time of the initial screening, disease progression, and often in longitudinal monitoring of molecular changes. Consequently, new potentially targetable molecular alterations have been identified in several different types of tumors, leading to the development of tumor-agnostic treatments. Being highly selective for specific molecular alterations, these drugs are active against different subtypes of oncogene-addicted cancers. Three of these drugs —pembrolizumab [an anti-programmed death 1 (PD-1) monoclonal antibody (MAb)], larotrectinib [a pan-tropomyosin receptor tyrosine kinase (TRK) inhibitor], and entrectinib [a pan-TRK, anaplastic lymphoma kinase (ALK) and ROS-1 inhibitor]—received US FDA approval in 2017, 2018, and 2019, respective ly. In this article, we critically review the clinical studies responsible for FDA approval and the most recently updated results. We then discuss the benefits and limitatio...
Source: Clinical Drug Investigation - Category: Drugs & Pharmacology Source Type: research