The American Society of Clinical Oncology (ASCO) recently updated its living guidelines, Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations and Therapy for Stage IV Non-Small Cell Lung Cancer Without Driver Alterations to version 2025.1. Since 2022, this pair of living guidelines have received regular updates, as needed. 

Today we’re taking a look at the latest couple of updates to both living guidelines, as well as a brief look back at the timeline of updates, dating back to November of 2024.

Latest Updates to ASCO Stage 4 NSCLC With and Without Driver Alterations Guidelines 

Therapy for Stage IV Non-Small-Cell Lung Cancer with Driver Alterations:

July 17, 2025 – Version 2025.1: A review of two new studies led to updated recommendations for first- and second-line treatment options. 

  • First-Line Treatment Options – Recommendation 1.1.1: Clinicians may offer osimertinib with platinum doublet chemotherapy or amivantamab plus lazertinib (Evidence quality: Moderate; Strength of recommendation: Weak).
  • Second-Line Treatment Options – Recommendation 2.20: Clinicians may offer zenocutuzumab (Evidence quality: Low; Strength of recommendation: Strong).

Therapy for Stage IV Non-Small-Cell Lung Cancer without Driver Alterations:

July 17, 2025 – Version 2025.1: A review of three new studies led to updated recommendations for first- and second-line treatment options.

First-Line Treatment Options for Patients with Good Performance Status, Any Histology, and Any PD-L1 Expression – Recommendations 1.5, 2.0, 2.6, 3.4, 3.8, 4.3: Clinicians may offer nivolumab and ipilimumab plus two cycles of platinum-based chemotherapy (Evidence quality: Moderate; Strength of recommendation: Weak). 

Second-Line and Subsequent Treatment Options – Recommendation 5.1: Clinicians should offer docetaxel with or without ramucirumab if the patient has already received platinum-based chemotherapy (Evidence quality: Low; Strength of recommendation: Strong). 

Timeline of Previous Versions

Therapy for Stage IV Non-Small-Cell Lung Cancer with Driver Alterations:

February 27, 2025 – Version 2024.3 updated the following recommendations:

  • Recommendation 1.1.1: Clinicians may offer osimertinib with platinum doublet chemotherapy or amivantamab plus lazertinib (Evidence quality: Moderate; Strength of recommendation: Weak).
  • Recommendation 2.2: For patients whose disease has progressed on osimertinib or other EGFR TKIs without emergent T790M or other targetable alterations, clinicians may offer platinum-based chemotherapy with or without amivantamab (Evidence quality: Moderate; Strength of recommendation: Strong).
  • Recommendation 2.2.2: For patients who have progressive disease on EGFR TKI, anti–PD-(L)1 agents with or without platinum chemotherapy are not recommended (Evidence quality: High; Strength of recommendation: Strong).

November 12, 2024 – Version 2024.2 updated the following recommendations:

  • Recommendation 1.1: Clinicians should offer osimertinib (Evidence quality: Moderate; Strength of recommendation: Strong).
  • Recommendation 1.1.1: Clinicians may offer osimertinib with platinum doublet chemotherapy or amivantamab plus lazertinib (Evidence quality: Moderate; Strength of recommendation: Weak).
  • Recommendation 2.2: For patients who have progressive disease on osimertinib or other EGFR tyrosine kinase inhibitors (TKIs) without emergent T790M or other targetable alterations, clinicians may offer platinum-based chemotherapy with or without amivantamab (Evidence quality: Moderate; Strength of recommendation: Strong).
  • Recommendation 2.2.2: For patients who have progressive disease on EGFR TKI, anti-PD-(L)1 agents with or without platinum chemotherapy are not recommended (Evidence quality: High; Strength of recommendation: Strong).

Therapy for Stage IV Non-Small-Cell Lung Cancer without Driver Alterations

February 27, 2025 – Version 2024.3 updated the following recommendation:

  • Recommendation 5.3: Clinicians may offer trastuzumab deruxtecan for patients with human epidermal growth factor receptor 2 (HER2)–overexpressing NSCLC defined as HER2 immunohistochemistry (IHC) 3+ (by gastric scoring). (Evidence quality: Very Low; Strength of recommendation: Weak).

February 28, 2024 – Version 2023.3 consolidated the previous guideline's recommendations. The recommendations remained unchanged in this version, with noted adjustments made to the quality of some evidence levels.

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