Treatment

Document Overview

Design and created by Guideline Central in participation with the American Society of Clinical Oncology.

Stage IV Non-Small Cell Lung Cancer without Driver Alterations

American Society of Clinical Oncology

Publication Date: Feb 3, 2026

Page Last Updated: May 5, 2026

Recommendation Rating Definitions

Quality of Evidence
Term		Definitions
H	- High	We are very confident that the true effect lies close to that of the estimate of the effect
M	- Moderate	We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
L	- Low	Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.
VL	- Very Low	We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
Ins	- Insufficient	Evidence is insufficient to discern the true magnitude and direction of the net effect. Further research may better inform the topic. Reliance on consensus opinion of experts may be reasonable to provide guidance on the topic until better evidence is available.

Strength of Recommendation
Term		Definitions
S	- Strong	In recommendations for an intervention, the desirable effects of an intervention outweigh its undesirable effects. In recommendations against an intervention, the undesirable effects of an intervention outweigh its desirable effects. All or almost all informed people would make the recommended choice for or against an intervention.

C W	- Conditional - Weak	In recommendations for an intervention, the desirable effects probably outweigh the undesirable effects, but appreciable uncertainty exists. In recommendations against an intervention, the undesirable effects probably outweigh the desirable effects, but appreciable uncertainty exists. Most informed people would choose the recommended course of action, but a substantial number would not.
GPS	Good Practice Statement	Good practice statements represent the consensus of the Expert Panel and are used when high quality indirect evidence is available, but it would not be a good use of the Expert Panel’s resources to conduct a formal systematic review
NR	- Not Rated

Brozek JL, Akl EA, Compalati E, et al: Grading quality of evidence and strength of recommendations in clinical practice guidelines part 3 of 3. The GRADE approach to developing recommendations. Allergy 66:588-95, 2011

Document Overview

Document Title: Stage IV Non-Small Cell Lung Cancer without Driver Alterations

Authoring Society: American Society of Clinical Oncology

Document Publication Date: Feb 3, 2026

Page Last Reviewed/Updated: May 5, 2026

Document Type: Guideline

Country of Publication: United States

Full Text Freely Available: Yes

Full Text Guideline: ascopubs.org/doi/10.1200/JCO-25-02825

Source Citation: Reuss JE, Bazhenova L, Ismaila N, et al. Therapy for Stage IV Non-Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2026.3.0. J Clin Oncol. 2026 Feb 03. doi: 10.1200/JCO-26-02825

Supplemental Implementation Resources

Document Scope, Criteria, and Use Cases

Document Objectives: To provide evidence-based recommendations for patients with stage IV non–small cell lung cancer (NSCLC) without driver alterations.

Scope: Treatment

Keywords: NSCLC, lung cancer, non-small-cell lung cancer, non-small-cell lung carcinoma (NSCLC)

Target Patient Population: Patients with stage IV NSCLC without driver alterations

Target Provider Population: Oncology care providers including primary care physicians, specialists, nurses, social workers, and others

Inclusion Criteria: Male, Female, Adolescent, Adult, Child, Older Adult

Health Care Settings: Ambulatory, Outpatient

Intended Users: Nurse, Nurse Practitioner, Physician, Physician Assistant, Social Worker

Recommendation Development Processes & Methodology

PICO Questions

What are the most effective second-line and subsequent treatment options for patients with stage IV NSCLC without driver alterations based on cancer subtype?

Supplemental Methodology Resource: Data Supplement

Number of Source Documents: 58

Literature Search Start Date: Thursday, December 10, 2015

Literature Search End Date: Sunday, September 9, 2018

Includes peer/external review process?: Yes

Includes public comment process?: Yes

Methodologist involvement?: Yes

Patient involvement?: Yes

Includes multi-disciplinary group?: Yes

Includes systematic review?: Yes

Grades quality of strength of evidence?: Yes

Grades quality of strength of recommendation?: Yes

Discloses funding source?: Yes

Discloses conflicts of interest?: Yes

Includes benefits/harms analysis with recommendations?: Yes

Identifies study selection process?: Yes

Identifies study selection criteria?: Yes

Identifies methods used to evaluate and analyze the evidence?: Yes

Identifies key questions addressed by the systematic review?: Yes

Identifies search strategy?: Yes

Stage IV Non-Small Cell Lung Cancer without Driver Alterations

Treatment

Summary of All Recommendations

Clinical Question 1: What are the most effective first-line treatment options for patients with good performance status and the following biomarkers:

Biomarker testing

Non-Squamous Cell Carcinoma (Non-SCC)

PD-L1 expression tumor proportion score (TPS) ≥50%

Clinicians should offer any of the following single agent immune checkpoint inhibitors:

Other combination regimens that may be offered in select instances include:

PD-L1 expression, TPS 1%–49%

Clinicians should offer any of the following combination immune checkpoint inhibitor and chemotherapy regimens:

Other combination regimens that may be offered in select instances includes:

Unknown or negative PD-L1 expression, TPS <1%

Clinicians may offer any of the following:

Squamous Cell Carcinoma (SCC)

PD-L1 expression, TPS ≥50%

Clinicians should offer treatment with single agent immune checkpoint inhibitors:

Other combination regimens that may be offered in select instances includes:

PD-L1 expression, TPS 1%–49%

Clinicians should offer any of the following combination immune checkpoint inhibitor and chemotherapy regimens:

Unknown or negative PD-L1 expression, TPS <1%

Clinicians may offer any of the following:

General Approaches

Patients with contraindications to bevacizumab

Clinical Question 2: What are the most effective second-line and subsequent treatment options for patients with good performance status:

Patients previously treated with immune checkpoint therapy without chemotherapy

Patients previously treated with chemotherapy and immune checkpoint therapy

Recommendation Rating Definitions

Document Overview

Supplemental Implementation Resources

Document Scope, Criteria, and Use Cases

Recommendation Development Processes & Methodology