Treatment of Advanced Non-Small Cell Lung Cancer in the Era of Targeted Therapy
Purpose of Review
Since the identification of multiple mutations associated with advanced non-small cell lung cancer (NSCLC), many targeted therapies have been developed for the treatment of this subgroup of lung cancers. These targeted therapies have changed the landscape of lung cancer treatment when compared to standard chemotherapy, with improved survival and quality of life. In this review article, we will review the major mutations associated with advanced NSCLC, namely EGFR, ALK, and ROS1. We will discuss their discovery, their clinical significance, and the diagnostic tests used for their detection. We will also review the respective targeted therapies developed, and the clinical trials that led to their approval.
We will also review the most recent advances in targeted therapies in the treatment of advanced NSCLC, including recent data on tyrosine kinase inhibitor osimertinib showing equal effectiveness to other first-line therapy and accordingly recommended in first line for EGFR-positive advanced NSCLC. We will discuss emerging targetable mutations such as HER2, RET, and MET.
Targeted therapies will likely shape the future of NSCLC treatment. They have been shown to provide survival advantage over chemotherapy, while providing better quality of life through ease of administration (most are oral drugs), as well as tolerability and better toxicity profile. Further elucidation of these and mutations may provide for future more effective targeted therapies.
KeywordsNon-small cell lung cancer (NSCLC) Tyrosine kinase inhibitors (TKI) Lung adenocarcinoma Anaplastic lymphoma kinase (ALK) Epidermal growth factor (EGFR) Targeted therapy C-ros mutation (ROS1) Rearranged during transfection (RET) Mesenchymal epithelial transition factor (MET) BRAF
Thanks are due to Dr. Shirin Shafazand for helping to review this paper.
Compliance with Ethical Standards
Conflict of Interest
Raja Mudad is on the advisory board for Novartis, Astra Zeneca, Takeda, and Guardant Health.
Mohamad Masri and Martine McManus declare no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: •• Of major Importance
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