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

Publication Date: February 28, 2024
Last Updated: February 29, 2024

Treatment

Clinical Question 1: What are the most effective first-line treatment options for patients’ status based on the driver alterations:

NOTE:
  • For recommendations with multiple treatment options of the same evidence quality and strength of recommendation, the decision of which agent to offer should be tailored to each patient incorporating both efficacy and toxicity.
  • All biomarkers should be available at the time of decision-making.

Epidermal growth factor receptor (EGFR)

Exon 19 deletion, Exon 21 L858R substitution
1.1. Clinicians should offer osimertinib. ( EB , , H , S )
Qualifying Statement: Although Recommendation 1.1 addresses many patients in the target population, the guideline manuscript presents additional options that may be reasonable, based on the evidence reviewed. In addition, use of osimertinib in patients previously treated with adjuvant tyrosine kinase inhibitors (TKIs) is not reflected in this guideline.
618
Others
1.2. For other activating EGFR alterations, (G719X, L861Q, S768I), clinicians may offer afatinib. ( EB , , L , S )
618
1.2.1. or osimertinib. ( IC , , L , W )
618
1.2.2. or standard treatment following the non-driver alteration guideline. ( IC , , L , W )
618
Qualifying Statement: Recommendation 1.2, 1.2.1, and 1.2.2 excludes exon 20 insertion alterations, T790M.
1.3. For any activating EGFR alteration, regardless of programmed death ligand 1 (PD-L1) expression levels (including exon 20 insertions), single-agent immune checkpoint inhibitors should not be offered as first-line therapy. ( EB , , M, S )
618
Exon 20 insertions
1.4. Clinicians may offer chemotherapy and amivantamab. ( EB , , M, S )
618
1.5. If amivantamab is not available, clinicians should offer standard treatment following the non-driver alteration guideline. ( EB , , M, S )
618

Anaplastic lymphoma kinase (ALK)

1.6. Clinicians should offer alectinib or brigatinib or lorlatinib. ( EB , , H , S )
618
1.7. If alectinib, brigatinib, or lorlatinib are not available, clinicians should offer ceritinib or crizotinib. ( EB , , H , S )
618

ROS1

1.8. Clinicians may offer crizotinib or entrectinib. ( EB , , M, S )
618
1.9. If crizotinib or entrectinib are not available or not tolerated, clinicians may offer ceritinib or lorlatinib. ( EB , , L , W )
618

BRAFV600E

1.10. Clinicians may offer dabrafenib and trametinib, or encorafenib and binimetinib. ( EB , , L , S )
618
1.11. If dabrafenib and trametinib, or encorafenib and binimetinib are not available, clinicians may offer standard first-line therapy following the non-driver alteration guideline. ( IC , , L , S )
618

MET exon 14 skipping mutation

1.12. Clinicians may offer capmatinib or tepotinib. ( EB , , L , S )
618
1.13. If capmatinib or tepotinib is not available, clinicians may offer standard first-line therapy following the non-driver alteration guidelines. ( IC , , L , S )
618

RET rearrangement

1.14. Clinicians should offer selpercatinib. ( EB , , H , S )
618
1.15. If selpercatinib is not available, clinicians may offer pralsetinib. ( EB , , M, S )
618
1.16. If selpercatinib or pralsetinib are not available, clinicians may offer standard therapy following the non-driver alteration guideline. ( IC , , L , W )
618

Neurotrophic tyrosine receptor kinase (NTRK) rearrangement

1.17. Clinicians may offer entrectinib or larotrectinib. ( EB , , L , S )
618
1.18. If entrectinib or larotrectinib are not available, clinicians may offer standard therapy following the non-driver alteration guideline. ( IC , , L , W )
618
1.19. For patients with a poor performance status (PS), tyrosine kinase inhibitor may be offered based on drug access and toxicity profile. ( IC , , L , W )
618
1.20. Comprehensive genomic biomarker test results should be available and used to guide treatment. ( EB , , H , S )
618
Qualifying Statement: PDL-1 IHC alone should not be used to guide treatment decisions.
1.21. Patients with advanced lung cancer should be referred to interdisciplinary palliative care teams (consultation) that provide inpatient and outpatient care early in the course of disease, alongside active treatment of their cancer. ( EB , , H , S )
618

Clinical Question 2: What are the most effective second-line and subsequent treatment options for patients based on the driver alterations:

NOTE:
  • Due to development of potentially targetable resistance mechanisms, every effort should be made to assess for presence of new mutation by tissue and/or blood next-generation sequencing (NGS) testing.
  • If patients have received all targeted options, or if no targeted options are available, clinicians may offer standard therapy following the non-driver alteration guideline.

EGFR

Exon 19 deletion, Exon 21 L858R substitution
2.1. For patients that develop EGFR T790M resistance alterations in tumor after first- or second-generation EGFR TKIs, clinicians should offer osimertinib. ( EB , , H , S )
618
2.2. For patients who have progressed on osimertinib or other EGFR TKIs without emergent T790M or other targetable alterations, clinicians should offer platinum-based chemotherapy following the non-driver alteration guideline. ( EB , , M, S )
618
Qualifying Statement: Anti-PD-(L)1 agents with platinum chemotherapy are not recommended although other emerging combination strategies may be considered and are discussed in the manuscript.
Others
2.3. For patients with an exon 20 insertion alteration who have received prior treatment with platinum chemotherapy, clinicians may offer treatment with amivantamab. ( EB , , L , S )
618

ALK

2.4. For patients who have previously received crizotinib, clinicians should offer alectinib, brigatinib, or ceritinib and may offer lorlatinib. ( EB , , M, S )
618
2.5. For patients who have previously received other ALK inhibitors including alectinib or brigatinib, clinicians may offer lorlatinib. ( EB , , L , S )
618

ROS1

2.6. For patients who have previously received crizotinib or entrectinib or ceritinib, clinicians may offer lorlatinib. ( EB , , L , W )
618
2.7. Clinicians should offer platinum-based chemotherapy following the non-driver alteration guideline. ( IC , , L , S )
618

BRAFV600E

2.8. For patients who have not received BRAF therapy, clinicians may offer dabrafenib and trametinib or encorafenib and binimetinib. ( EB , , L , S )
618
2.9. For patients who have previously received BRAF or MEK targeted therapy, clinicians should offer standard first-line therapy following the non-driver alteration guideline. ( IC , , L , S )
618
2.10. For BRAF alterations other than BRAFV600E alterations, clinicians should offer standard therapy following the non-driver alteration guideline. ( IC , , L , S )
618

MET exon 14 skipping mutation

2.11. For patients who have not received MET-targeted therapy, clinicians may offer capmatinib or tepotinib. ( EB , , L , S )
618
2.12. For patients previously treated with MET-targeted therapy, clinicians should offer standard therapy following the non-driver alteration guideline. ( IC , , L , S )
618

RET rearrangement

2.13. For patients who have not received a RET inhibitor, clinicians should offer selpercatinib or pralsetinib. ( EB , , M, S )
618
2.14. If selpercatinib or pralsetinib is not available, clinicians may offer treatment following the non-driver alteration guideline. ( IC , , L , S )
618

NTRK rearrangement

2.15. For patients who have not received an NTRK inhibitor, clinicians should offer entrectinib or larotrectinib. ( EB , , L , S )
618
2.16. If entrectinib or larotrectinib is not available, clinicians may offer standard therapy following the non-driver alteration guideline. ( IC , , L , S )
618

Human epidermal receptor factor 2 (HER2)

2.17. Clinicians may offer treatment with trastuzumab deruxtecan. ( EB , , L , S )
618

KRAS G12C

2.18. Clinicians may offer treatment with sotorasib. ( EB , , M, S )
618
2.19. Clinicians may offer treatment with adagrasib. ( EB , , L , S )
618
Qualifying Statement: Note that adagrasib and sotorasib are approved for patients who have received prior chemotherapy and/or anti-PD-(L)1 for patients with advanced KRAS G12C mutant NSCLC. In the first-line setting, these patients should be offered standard first-line treatment with immune checkpoint inhibitor therapy and/or chemotherapy following the non-driver alteration guideline.

Recommendation Grading

Overview

Title

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

Authoring Organization

Publication Month/Year

February 28, 2024

Last Updated Month/Year

February 29, 2024

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Inclusion Criteria

Male, Female, Adult

Health Care Settings

Ambulatory, Home health, Hospital, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant, social worker

Scope

Treatment, Management

Diseases/Conditions (MeSH)

D002289 - Carcinoma, Non-Small-Cell Lung

Keywords

non-small cell lung cancer, Targeted Therapy, Clinical guidelines, ROS-1 fusions, BRAF V600e mutations, RETfusions, MET exon 14 skipping mutations, NTRK fusions

Source Citation

Jaiyesimi IA, Leighl NB, Ismaila N, et al. Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2023.3. JCO Glob Oncol. 2024 Feb 28. doi: 10.1200/JCO.23.02744

Supplemental Methodology Resources

Data Supplement

Methodology

Number of Source Documents
174
Literature Search Start Date
December 3, 2015
Literature Search End Date
February 6, 2023