As reported in the Journal of Clinical Oncology by Gregory A. Masters, MD, and colleagues, ASCO has issued a clinical practice guideline update on systemic therapy for stage IV non–small cell lung cancer (NSCLC).¹ Recommendations are based on an update committee systematic review of randomized controlled trials conducted between January 2007 and February 2014. The update committee was co-chaired by David H. Johnson, MD, of the University of Texas Southwestern Medical Center at Dallas, and Dr. Masters, of the Helen F. Graham Cancer Center, Newark, Delaware.

The basic recommendations are reproduced here. For all recommendations, benefits outweigh the harms. The type of recommendation is evidence based, except where otherwise noted.

Overall

• There is no cure for patients with stage IV NSCLC.
• Decisions on chemotherapy should not be made on the basis of age alone.

First-Line Treatment

• For patients without an epidermal growth factor receptor (EGFR)-sensitizing mutation or ALK gene re­arrangement and a performance status of 0 to 1 (or appropriate patients with a performance status of 2): A variety of combination cytotoxic chemotherapies are recommended. Platinum-based doublets are preferred, along with early concurrent palliative care and symptom management. Based on tumor histology (ie, squamous vs nonsquamous), there are some variations (evidence quality = high, strength of recommendation = strong).
• Adding bevacizumab (Avastin) to carboplatin plus paclitaxel is recommended if there are no contraindications (evidence quality = intermediate, strength of recommendation = moderate).
• For patients with a performance status of 2: Combination or single-agent chemotherapy or palliative care alone may be used (for chemotherapy: evidence quality = intermediate, strength of recommendation = weak; for palliative care: evidence quality = intermediate, strength of recommendation = strong).
• For patients with sensitizing EGFR mutations: Afatinib (Gilotrif), erlotinib (Tarceva), or gefitinib is recommended (evidence quality = high, strength of recommendation = strong for each).
• For patients with ALK gene rearrangements: Crizotinib (Xalkori) is recommended (evidence quality = intermediate, strength of recommendation = moderate).
• For patients with ROS1 rearrangement: Crizotinib is recommended (recommendation type = informal consensus, evidence quality = low, strength of recommendation = weak).
• For patients with large cell neuroendocrine carcinoma: Platinum plus etoposide or the same treatment as other patients with nonsquamous carcinoma may be administered (recommendation type = informal consensus, evidence quality = low, strength of recommendation = weak).
• First-line cytotoxic chemotherapy should be stopped at disease progression or after four cycles in patients with nonresponsive stable disease (no change in recommendation).
• For patients with stable disease or response after four cycles of a first-line pemetrexed (Alimta)-containing regimen: Pemetrexed continuation maintenance may be used; if initial regimen does not contain pemetrexed, an alternative chemotherapy (switch) may be used, or a break from chemotherapy may be recommended until disease progression (for addition of pemetrexed: evidence quality = intermediate, strength of recommendation = moderate).

Second-Line Treatment

• For patients with nonsquamous cell carcinoma: Docetaxel, erlotinib, gefitinib, or pemetrexed is acceptable (evidence quality = high, strength of recommendation = strong).
• For patients with squamous cell carcinoma: Docetaxel, erlotinib, or gefitinib is acceptable (evidence quality = high, strength of recommendation = strong).
• For patients with sensitizing EGFR mutations who did not respond to a first-line EGFR tyrosine kinase inhibitor: Combination cytotoxic chemotherapy is recommended for those with nonsquamous cell carcinoma, as listed under first-line treatment (recommendation type = informal consensus, evidence quality = intermediate, strength of recommendation = strong).
• For patients with sensitizing EGFR mutations who received a first-line EGFR tyrosine kinase inhibitor and experienced disease progression after an initial response: Regimen may be switched to chemotherapy or another EGFR tyrosine kinase inhibitor as second-line therapy (recommendation type = informal consensus, evidence quality = low, strength of recommendation = weak).
• For patients with ALK rearrangement and progression after first-line crizotinib: Chemotherapy or ceritinib (Zykadia) may be offered (for chemotherapy: evidence quality = high, strength of recommendation = strong; for ceritinib: evidence quality = intermediate, strength of recommendation = moderate).

Third-Line Treatment

• For patients who have not received erlotinib or gefitinib and have a performance status of 0 to 3: Erlotinib may be recommended.
• Data are insufficient to recommend routine third-line cytotoxic drugs.

Additional information is available at http://www.asco.org/guidelines/nsclc. Patient information is available at http://www.cancer.net. ■

Disclosure: For full disclosures of the authors, visit jco.ascopubs.org.

Reference

1. Masters GA, Temin S, Azzoli CG, et al: Systemic therapy for stage IV non-small-cell lung cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 33:3488-3515, 2015.

See here for commentary by Heather A. ­Wakelee, MD.