Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations
Treatment
Summary of All Recommendations
- 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.
(, , H , S )1.1.1.
or may offer osimertinib with chemotherapy.
(, , 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.
Others
1.2.
1.2.1.
or osimertinib.
(, , L , W )Qualifying Statement: Recommendation 1.2, 1.2.1, and 1.2.2 excludes exon 20 insertion alterations, T790M.
1.2.2.
1.3.
Exon 20 insertions
1.4.
Clinicians may offer chemotherapy and amivantamab.
(, , M, S )1.5.
Anaplastic lymphoma kinase (ALK)
1.6.
1.7.
ROS1
1.8
Clinicians may offer repotrectinib, entrectinib, or crizotinib.
(, , M, S )1.9
If crizotinib, entrectinib, or repotrectinib are not available or not tolerated, clinicians may offer ceritinib or lorlatinib.
(, , L , W )BRAFV600E
1.10.
1.11.
MET exon 14 skipping mutation
1.12.
1.13.
RET rearrangement
1.14.
1.15.
If selpercatinib is not available, clinicians may offer pralsetinib.
(, , M, S )1.16.
Neurotrophic tyrosine receptor kinase (NTRK) rearrangement
1.17.
Clinicians may offer entrectinib or larotrectinib.
(, , L , S )1.18.
1.19.
1.20.
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 )Clinical Question 2: What are the most effective second-line and subsequent treatment options for patients based on the driver alterations:
- 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 )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.
(, , M, S )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.
2.2.1
For patients who progressed on osimertinib (or other 3rd generation TKI), clinicians may offer amivantamab plus carboplatin and pemetrexed.
(, , M, S )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.
ALK
2.4.
For patients who have previously received crizotinib, clinicians should offer alectinib, brigatinib, or ceritinib and may offer lorlatinib.
(, , M, S )2.5.
ROS1
2.6
For patients who have previously received crizotinib, entrectinib, lorlatinib, or ceritinib, clinicians may offer repotrectinib.
(, , M, S )2.7
BRAFV600E
2.8.
For patients who have not received BRAF therapy, clinicians may offer dabrafenib and trametinib or encorafenib and binimetinib.
(, , L , S )2.9.
2.10.
For BRAF alterations other than BRAFV600E alterations, clinicians should offer standard therapy following the non-driver alteration guideline.
(, , L , S )MET exon 14 skipping mutation
2.11.
2.12.
For patients previously treated with MET-targeted therapy, clinicians should offer standard therapy following the non-driver alteration guideline.
(, , L , S )RET rearrangement
2.13.
2.14.
NTRK rearrangement
2.15.
2.16.
If entrectinib or larotrectinib is not available, clinicians may offer standard therapy following the non-driver alteration guideline.
(, , L , S )Human epidermal receptor factor 2 (HER2)
2.17.
Clinicians may offer treatment with trastuzumab deruxtecan.
(, , L , S )KRAS G12C
2.18
2.19
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
May 29, 2024
Last Updated Month/Year
October 21, 2024
Supplemental Implementation Tools
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
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