Systemic Therapy for Locally Advanced and Metastatic Non–Small Cell Lung Cancer: A Review

IMPORTANCE: Non–small cell lung cancer remains the leading cause of cancer death in the United States. Until the last decade, the 5-year overall survival rate for patients with metastatic non–small cell lung cancer was less than 5%. Improved understanding of the biology of lung cancer has resulted i...

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Bibliographic Details
Published in:JAMA : the journal of the American Medical Association 2019-08, Vol.322 (8), p.764-774
Main Authors: Arbour, Kathryn C, Riely, Gregory J
Format: Article
Language:English
Subjects:
ALK protein
Apoptosis
Biology
Biomarkers
Cancer therapies
Carboplatin
Chemotherapy
Cisplatin
Cytotoxicity
Enzyme inhibitors
Epidermal growth factor receptors
Gefitinib
Immune checkpoint inhibitors
Inhibitors
Kinases
Lung cancer
Medical treatment
Metastases
Metastasis
Mutation
PD-L1 protein
Platinum
Protein-tyrosine kinase
Proteins
Survival
Tumors
Tyrosine
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Summary:IMPORTANCE: Non–small cell lung cancer remains the leading cause of cancer death in the United States. Until the last decade, the 5-year overall survival rate for patients with metastatic non–small cell lung cancer was less than 5%. Improved understanding of the biology of lung cancer has resulted in the development of new biomarker–targeted therapies and led to improvements in overall survival for patients with advanced or metastatic disease. OBSERVATIONS: Systemic therapy for metastatic non–small cell lung cancer is selected according to the presence of specific biomarkers. Therefore, all patients with metastatic non–small cell lung cancer should undergo molecular testing for relevant mutations and expression of the protein PD-L1 (programmed death ligand 1). Molecular alterations that predict response to treatment (eg, EGFR mutations, ALK rearrangements, ROS1 rearrangements, and BRAF V600E mutations) are present in approximately 30% of patients with non–small cell lung cancer. Targeted therapy for these alterations improves progression-free survival compared with cytotoxic chemotherapy. For example, somatic activating mutations in the EGFR gene are present in approximately 20% of patients with advanced non–small cell lung cancer. Tyrosine kinase inhibitors such as gefitinib, erlotinib, and afatinib improve progression-free survival in patients with susceptible EGFR mutations. In patients with overexpression of ALK protein, the response rate was significantly better with crizotinib (a tyrosine kinase inhibitor) than with the combination of pemetrexed and either cisplatin or carboplatin (platinum-based chemotherapy) (74% vs 45%, respectively; P 
ISSN:0098-7484
1538-3598
DOI:10.1001/jama.2019.11058