医学
克里唑蒂尼
肺癌
吉非替尼
培美曲塞
埃罗替尼
卡铂
ROS1型
肿瘤科
靶向治疗
内科学
阿法替尼
癌症研究
间变性淋巴瘤激酶
癌症
化疗
表皮生长因子受体
腺癌
顺铂
恶性胸腔积液
作者
Kathryn C. Arbour,Gregory J. Riely
出处
期刊:JAMA
[American Medical Association]
日期:2019-08-27
卷期号:322 (8): 764-764
被引量:739
标识
DOI:10.1001/jama.2019.11058
摘要
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,EGFRmutations,ALKrearrangements,ROS1rearrangements, andBRAFV600E 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 theEGFRgene 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 susceptibleEGFRmutations. 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 < .001) and progression-free survival (median, 10.9 months vs 7.0 months;P < .001). Subsequent generations of tyrosine kinase inhibitors have improved these agents. For patients without biomarkers indicating susceptibility to specific targeted treatments, immune checkpoint inhibitor–containing regimens either as monotherapy or in combination with chemotherapy are superior vs chemotherapy alone. These advances in biomarker-directed therapy have led to improvements in overall survival. For example, the 5-year overall survival rate currently exceeds 25% among patients whose tumors have high PD-L1 expression (tumor proportion score of ≥50%) and 40% among patients withALK-positive tumors. Conclusions and Relevance
Improved understanding of the biology and molecular subtypes of non–small cell lung cancer have led to more biomarker-directed therapies for patients with metastatic disease. These biomarker-directed therapies and newer empirical treatment regimens have improved overall survival for patients with metastatic non–small cell lung cancer.
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