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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Rare driver alterations in nonsmall cell lung cancer: novel targeted drugs
Diego Kauffmann-Guerrero1, Amanda Tufman
1Department of Medicine V, Thoracic Oncology Centre Munich (TOM), University Hospital, LMU Munich, Munich, Germany.
Purpose Of Review:
The current review presents clinically relevant driver alterations in nonsmall cell lung cancer (NSCLC) and the targeted treatments currently available for clinical use as well as those in clinical trials and advanced stages of drug development.
Recent Findings:
Mesenchymal-epithelial transition factor, human epidermal growth factor receptor 2, proto-oncogene B-RAF (BRAF), proto-oncogene tyrosine-protein kinase ROS (ROS1), rearranged during transfection (RET) and neurotrophic tyrosine kinase are rare genetic driver alterations, each present in a small subset of patients with NSCLC. Treatments targeting BRAF, ROS1, RET and neurotrophic tyrosine kinase are approved in Europe, and promising treatments targeting mesenchymal-epithelial transition factor and human epidermal growth factor receptor 2 are available in clinical trials and compassionate use programs. The response rates, duration of response and tolerability observed in trials of targeted drugs in this setting are presented in detail here.
Summary:
While rare driver alterations are, by definition, rare, their recognition can change the course of NSCLC for those patients affected. Targeted treatments for many rare driver alterations are well tolerated and effective. Screening for molecular changes in advanced NSCLC should include screening for rare drivers, and patients should be directed to clinical trials in setting where treatment of the driver alterations is not otherwise available.
Insights
Identifying rare genetic drivers in nonsmall cell lung cancer (NSCLC) is crucial. Targeted therapies for these alterations show promise, improving outcomes for affected patients.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Nonsmall cell lung cancer (NSCLC) harbors various genetic alterations.
- Identifying rare driver mutations is key for personalized treatment strategies.
Purpose of the Study:
- To review clinically relevant driver alterations in NSCLC.
- To discuss targeted treatments available and in development for these rare alterations.
Main Methods:
- Literature review of current clinical data.
- Analysis of targeted therapies for specific genetic drivers.
Main Results:
- Rare drivers include MET, ERBB2, BRAF, ROS1, RET, and NTRK.
- Approved and investigational therapies show efficacy and tolerability.
- Response rates and duration of response data are detailed.
Conclusions:
- Recognition of rare drivers can significantly alter NSCLC patient outcomes.
- Targeted treatments for rare drivers are effective and well-tolerated.
- Screening for rare drivers and enrollment in clinical trials are recommended.
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