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: May 28, 2026

Page Last Updated: Jul 17, 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.

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.
W	- 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.

GRADE Handbook, Schünemann, et al. 2013.

Document Overview

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

Authoring Society: American Society of Clinical Oncology

Document Publication Date: May 28, 2026

Page Last Reviewed/Updated: Jul 17, 2026

Document Type: Guideline

Country of Publication: United States

Full Text Freely Available: Yes

Full Text Guideline: ascopubs.org/guidelines/therapy-stage-iv-non-small-cell-lung-cancer-without-driver-alterations

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, 2026.3.0. J Clin Oncol. 2026;44(7):e56-e88. doi:10.1200/JCO-25-02825

Reuss JE, Bazhenova L, Ismaila N, et al. Therapy for stage IV non–small cell lung cancer without driver alterations: ASCO living guideline, 2026.3.2. Online ahead of print.

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

Diseases/Conditions (MeSH): D002289 - Carcinoma, Non-Small-Cell Lung

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

Biomarker Testing

Recommendation 1.0

First-Line Therapy

Non-squamous Cell Carcinoma (Non-SCC), PD-L1 Expression, Tumor Proportion Score (TPS) ≥50%

Recommendation 1.1

Recommendation 1.2

Recommendation 1.3

Recommendation 1.4

Recommendation 1.5

Recommendation 1.6

Recommendation 1.7

Recommendation 1.8

Non-SCC, PD-L1 Expression, TPS 1%–49%

Recommendation 1.9

Recommendation 1.10

Recommendation 1.11

Recommendation 1.12

Recommendation 1.13

Recommendation 1.14

Recommendation 1.15

Recommendation 1.16

Non-SCC, Unknown or Negative PD-L1 Expression, TPS <1%

Recommendation 1.17

Recommendation 1.18

Recommendation 1.19

Recommendation 1.20

Recommendation 1.21

Recommendation 1.22

Non-SCC, PD-L1 Expression, TPS 1%–49%

Recommendation 1.23

SCC, PD-L1 Expression, TPS ≥50%

Recommendation 2.1

Recommendation 2.2

Recommendation 2.3

Recommendation 2.4

Recommendation 2.5

SCC, PD-L1 Expression, TPS 1%–49%

Recommendation 2.6

Recommendation 2.7

Recommendation 2.8

Recommendation 2.9

Recommendation 2.10

Recommendation 2.11

SCC, Unknown or Negative PD-L1 Expression, TPS <1%

Recommendation 2.12

Recommendation 2.13

Recommendation 2.14

Recommendation 2.15

Recommendation 2.16

General Approaches

Recommendation 3.1

Recommendation 3.2

Recommendation 3.3

Patients With Contraindications to Bevacizumab

Recommendation 3.4

Recommendation 3.5

Second-Line and Subsequent Therapies

Patients Previously Treated With Immune Checkpoint Therapy Without Chemotherapy

Recommendation 4.1

Patients Previously Treated With Chemotherapy and Immune Checkpoint Therapy

Recommendation 4.2

Recommendation 4.3

Recommendation 4.4

Recommendation 4.5

Recommendation Rating Definitions

Document Overview

Supplemental Implementation Resources

Document Scope, Criteria, and Use Cases

Recommendation Development Processes & Methodology