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

Publication Date: November 12, 2024
Last Updated: November 14, 2024

Treatment

Summary of All Recommendations

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.

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

Epidermal growth factor receptor (EGFR)
Exon 19 deletion, Exon 21 L858R substitution

1.1.

Clinicians should offer osimertinib.

(, , M, 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

1.1.1.

Clinicians may offer osimertinib with platinum doublet chemotherapy or amivantamab plus lazertinib.

(, , M, W )

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 or (, , L , S )
Qualifying Statement: Recommendation 1.2, 1.2.1, and 1.2.2 excludes exon 20 insertion alterations, T790M.
618

1.2.1.

For other activating EGFR alterations, (G719X, L861Q, S768I), clinicians may offer osimertinib or

(, , L , W )

Qualifying Statement: Recommendation 1.2, 1.2.1, and 1.2.2 excludes exon 20 insertion alterations, T790M.

618
1.2.2.
For other activating EGFR alterations, (G719X, L861Q, S768I), clinicians may offer standard treatment following the non-driver alteration guideline. (, , L , W )
Qualifying Statement: Recommendation 1.2, 1.2.1, and 1.2.2 excludes exon 20 insertion alterations, T790M.
618

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.

(, , M, S )
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Exon 20 insertions
1.4.
Clinicians may offer chemotherapy and amivantamab. (, , M, S )
618

1.5.

If amivantamab is not available, clinicians should offer standard treatment following the non-driver alteration guideline.

(, , M, S )
618

Anaplastic lymphoma kinase (ALK)

1.6.

Clinicians should offer alectinib or brigatinib or lorlatinib.

(, , H , S )
618

1.7.

If alectinib, brigatinib, or lorlatinib are not available, clinicians should offer ceritinib or crizotinib.

(, , H , S )
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ROS1

1.8.

Clinicians may offer repotrectinib, entrectinib, or crizotinib.

(, , M, S )
618

1.9.

If crizotinib, entrectinib, or repotrectinib are not available or not tolerated, clinicians may offer ceritinib or lorlatinib.

(, , L , W )
618
BRAFV600E
1.10.
Clinicians may offer dabrafenib and trametinib, or encorafenib and binimetinib. (, , 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. (, , L , S )
618

MET exon 14 skipping mutation

1.12.
Clinicians may offer capmatinib or tepotinib. (, , 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.

(, , L , S )
618
RET rearrangement

1.14.

Clinicians should offer selpercatinib.

(, , H , S )
618
1.15.
If selpercatinib is not available, clinicians may offer pralsetinib. (, , M, S )
618

1.16.

If selpercatinib or pralsetinib are not available, clinicians may offer standard therapy following the non-driver alteration guideline.

(, , L , W )
618
Neurotrophic tyrosine receptor kinase (NTRK) rearrangement

1.17.

Clinicians may offer entrectinib or larotrectinib.

(, , L , S )
618
1.18.
If entrectinib or larotrectinib are not available, clinicians may offer standard therapy following the non-driver alteration guideline. (, , 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.

(, , L , W )
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1.20.

Comprehensive genomic biomarker test results should be available and used to guide treatment.

(, , H , S )

Qualifying Statement: PDL-1 IHC alone should not be used to guide treatment decisions.

618
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. (, , H , S )
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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.

(, , H , S )
618

2.2.

For patients who have progressive disease on osimertinib or other EGFR TKIs without emergent T790M or other targetable alterations, clinicians may offer platinum-based chemotherapy with or without amivantamab.

(, , M, S )

Qualifying Statement: Patients that do not pursue amivantamab plus chemotherapy may also consider chemotherapy plus bevacizumab if they have adenocarcinoma and bevacizumab is deemed safe.

618

2.2.1.

For patients who progressed on osimertinib (or other 3rd generation TKI), clinicians may offer amivantamab plus carboplatin and pemetrexed.

(, , M, S )
618
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. (, , H , S )
618
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. (, , L , S )
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ALK

2.4.
For patients who have previously received crizotinib, clinicians should offer alectinib, brigatinib, or ceritinib and may offer lorlatinib. (, , M, S )
618

2.5.

For patients who have previously received other ALK inhibitors including alectinib or brigatinib, clinicians may offer lorlatinib.

(, , L , S )
618
ROS1

2.6.

For patients who have previously received crizotinib, entrectinib, lorlatinib, or ceritinib, clinicians may offer repotrectinib.

(, , M, S )
618
2.7.
For patients who have received multiple ROS-1 inhibitors, clinicians should offer platinum-based chemotherapy following the non-driver alteration guideline. (, , L , S )
618
BRAFV600E
2.8.
For patients who have not received BRAF therapy, clinicians may offer dabrafenib and trametinib or encorafenib and binimetinib. (, , 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.

(, , L , S )
618
2.10.

For BRAF alterations other than BRAFV600E alterations, clinicians should offer standard therapy following the non-driver alteration guideline.

(, , 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. (, , L , S )
618
2.12.
For patients previously treated with MET-targeted therapy, clinicians should offer standard therapy following the non-driver alteration guideline. (, , L , S )
618
RET rearrangement
2.13.
For patients who have not received a RET inhibitor, clinicians should offer selpercatinib or pralsetinib. (, , M, S )
618

2.14.

If selpercatinib or pralsetinib is not available, clinicians may offer treatment following the non-driver alteration guideline.

(, , L , S )
618
NTRK rearrangement

2.15.

For patients who have not received an NTRK inhibitor, clinicians should offer entrectinib or larotrectinib.

(, , L , S )
618
2.16.
If entrectinib or larotrectinib is not available, clinicians may offer standard therapy following the non-driver alteration guideline. (, , L , S )
618
Human epidermal receptor factor 2 (HER2)
2.17.
Clinicians may offer treatment with trastuzumab deruxtecan. (, , L , S )
618
KRAS G12C
2.18.
Clinicians may offer treatment with sotorasib. (, , M, S )
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.
618

2.19.

Clinicians may offer treatment with adagrasib.

(, , L , S )

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.

618

Recommendation Grading

Overview

Title

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

Authoring Organization

American Society of Clinical Oncology

Publication Month/Year

November 12, 2024

Last Updated Month/Year

November 14, 2024

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Target Patient Population

Patients with stage IV non–small cell lung cancer (NSCLC) with driver alterations

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

Source Bazhenova L, Ismaila N, Rous FA, et al. Therapy for Stage IV Non-Small Cell Lung Cancer with Driver Alterations: ASCO Living Guideline, Version 2024.2. J Clin Oncol. 2024 November 12. doi: 10.1200/JCO.24.02133

Owen DH, Ismaila N, Freeman-Daily J, et al. Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2024.1. J Clin Oncol. 2024 May 30. doi: 10.1200/JCO.24.00762

Supplemental Methodology Resources

Data Supplement

Methodology

Number of Source Documents
174
Literature Search Start Date
June 29, 2022
Literature Search End Date
January 18, 2024