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J Clin Oncol. 2015 Oct 20;33(30):3488-515. doi: 10.1200/JCO.2015.62.1342. Epub 2015 Aug 31.

Systemic Therapy for Stage IV Non-Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update.

Author information

Gregory A. Masters, Helen F. Graham Cancer Center, Newark, DE; Sarah Temin, American Society of Clinical Oncology, Alexandria; Sherman Baker Jr, Virginia Commonwealth University; David Trent, Virginia Cancer Center, Richmond, VA; Christopher G. Azzoli, Massachusetts General Hospital Cancer Center, Boston, MA; Giuseppe Giaccone, Lombardi Cancer Center, Georgetown University, Washington, DC; Julie R. Brahmer and Thomas J. Smith, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, MD; Peter M. Ellis, Juravinski Cancer Centre, Hamilton, Ontario, Canada; Ajeet Gajra, Upstate Medical University, Syracuse, NY; Nancy Rackear, Uniting Against Lung Cancer, Fort Lauderdale, FL; Joan H. Schiller, University of Texas Southwestern; David H. Johnson, University of Texas Southwestern Medical Center at Dallas, Dallas; and John R. Strawn, patient representative, Houston, TX.

Erratum in



To provide evidence-based recommendations to update the American Society of Clinical Oncology guideline on systemic therapy for stage IV non-small-cell lung cancer (NSCLC).


An Update Committee of the American Society of Clinical Oncology NSCLC Expert Panel based recommendations on a systematic review of randomized controlled trials from January 2007 to February 2014.


This guideline update reflects changes in evidence since the previous guideline.


There is no cure for patients with stage IV NSCLC. For patients with performance status (PS) 0 to 1 (and appropriate patient cases with PS 2) and without an EGFR-sensitizing mutation or ALK gene rearrangement, combination cytotoxic chemotherapy is recommended, guided by histology, with early concurrent palliative care. Recommendations for patients in the first-line setting include platinum-doublet therapy for those with PS 0 to 1 (bevacizumab may be added to carboplatin plus paclitaxel if no contraindications); combination or single-agent chemotherapy or palliative care alone for those with PS 2; afatinib, erlotinib, or gefitinib for those with sensitizing EGFR mutations; crizotinib for those with ALK or ROS1 gene rearrangement; and following first-line recommendations or using platinum plus etoposide for those with large-cell neuroendocrine carcinoma. Maintenance therapy includes pemetrexed continuation for patients with stable disease or response to first-line pemetrexed-containing regimens, alternative chemotherapy, or a chemotherapy break. In the second-line setting, recommendations include docetaxel, erlotinib, gefitinib, or pemetrexed for patients with nonsquamous cell carcinoma; docetaxel, erlotinib, or gefitinib for those with squamous cell carcinoma; and chemotherapy or ceritinib for those with ALK rearrangement who experience progression after crizotinib. In the third-line setting, for patients who have not received erlotinib or gefitinib, treatment with erlotinib is recommended. There are insufficient data to recommend routine third-line cytotoxic therapy. Decisions regarding systemic therapy should not be made based on age alone. Additional information can be found at and

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