ASCO Guideline on Stage IV NSCLC Therapy Updated

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Nasser Hanna, MD

Nasser Hanna, MD

Gregory Masters, MD, FACP, FASCO

Gregory Masters, MD, FACP, FASCO

An update of the ASCO clinical practice guideline on the systemic treatment of patients with stage IV non–small cell lung cancer (NSCLC) clarifies the role of immunotherapy in this setting. The update was published by Hanna et al in the Journal of Clinical Oncology.1

“This guideline update provides oncologists with the tools to choose therapies that are most likely to benefit their patients,” said Nasser Hanna, MD, Co-Chair of the expert panel that developed the guideline update.

ASCO published the previous guideline on systemic therapy for stage IV NSCLC in 2015.2 For this update, an expert panel with multidisciplinary representation reviewed medical literature published between February 2014 and December 2016. 

“Knowing when to use targeted therapies or immunotherapy in place of more toxic chemotherapy can help improve the quality of life of our patients,” said Gregory Masters, MD, FACP, FASCO, Co-Chair of the guideline panel. 

Key Recommendations

Key New recommendations from the guideline update include:

First-Line Therapy: For patients with EGFR mutation–negative, ALK rearrangement–negative, and ROS1 rearrangement–negative tumors:

  • Pembrolizumab (Keytruda) alone is recommended in patients with high programmed cell death ligand 1 (PD-L1) expression in the tumor (tumor proportion score ≥ 50%).
  • Other checkpoint inhibitors, combinations of checkpoint inhibitors, and immune checkpoint therapy with chemotherapy are not recommended.
  • If the patient has low PD-L1 expression (tumor proportion score < 50%), clinicians should offer standard chemotherapy.

For patients with EGFR mutation–positive, ALK rearrangement–positive, or ROS1 rearrangement–positive tumors, first-line recommendations for targeted therapy from the 2015 guideline remain the same.

Second-Line Therapy

  • For patients with high PD-L1 expression in the tumor, if there is no prior immunotherapy treatment, clinicians should use single-agent nivolumab (Opdivo), pembrolizumab, or atezolizumab (Tecentriq); if the tumor has low PD-L1 expression or the PD-L1 expression level is unknown, clinicians should use nivolumab, atezolizumab, or chemotherapy.
  • Other checkpoint inhibitors, combinations of checkpoint inhibitors, and immune checkpoint therapy with chemotherapy are not recommended. 
  • For patients who received immune checkpoint inhibitors as first-line therapy, clinicians should offer standard chemotherapy. For patients with a sensitizing EGFR mutation and progression following first-line EGFR-targeted therapy, osimertinib -(Tagrisso) is recommended if the tumor has the T790M point mutation; if the tumor lacks the T790M mutation, then chemotherapy is recommended.
  • Patients with ROS1 gene rearrangement who have not previously received crizotinib (Xalkori) may be offered crizotinib, or if they have had prior crizotinib, may be offered chemotherapy.
  • Concurrent palliative care is recommended starting at diagnosis. ■

DISCLOSURE: For full disclosures of the guideline update panel, visit


1. Hanna N, et al: J Clin Oncol. August 14, 2017 (early release online).

2. Masters GA, et al: J Clin Oncol 33:3488-3515, 2015




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