Last updated July 21, 2022

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

Treatment

Note: unless otherwise listed, recommendations apply to patients with a performance status of 0–2.

EGFR First-line

Recommendation 1.1

For patients with a sensitizing (L858R/exon 19 deletion, with or without a concomitant T790M mutation) EGFR mutation with stage IV NSCLC and a performance status of 0–2 who have not had previous systemic therapy, clinicians should offer osimertinib monotherapy. ( EB , B , 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. This statement applies to all recommendations with the word “should.” In addition, use of osimertinib in patients previously treated with adjuvant or consolidation tyrosine kinase inhibitors is not part of this guideline.
618

Recommendation 1.2

For patients with a sensitizing (L858R/exon 19 deletion) EGFR mutation with stage IV NSCLC and a performance status of 0–2, previously untreated with systemic therapy and for whom osimertinib is not available, clinicians may use combination gefitinib with doublet chemotherapy (platinum/pemetrexed with maintenance pemetrexed). ( EB , B , H , M )
618

Recommendation 1.3

For patients with a sensitizing (L858R/exon 19 deletion) EGFR mutation with stage IV NSCLC and a performance status of 0–2, previously untreated with systemic therapy and for whom osimertinib is not available, clinicians may use dacomitinib monotherapy. ( EB , B , H , M )
618

Recommendation 1.4

For patients with a sensitizing (L858R/exon 19 deletion) EGFR mutation with stage IV NSCLC and a performance status of 0–2, who have not had previous systemic therapy, and do not have access to osimertinib, clinicians may use monotherapy with afatinib or erlotinib/bevacizumab or erlotinib/ramucirumab. ( EB , B , I , M )
618

Recommendation 1.5

For patients with a sensitizing (L858R/exon 19 deletion) EGFR mutation with stage IV NSCLC and a performance status of 0–2, who have not had previous systemic therapy, and do not have access to other regimens, clinicians may use monotherapy with gefitinib, erlotinib, or icotinib. ( EB , B , I , M )
618

Recommendation 1.6

For patients with a sensitizing (L858R/exon 19 deletion) EGFR mutation with stage IV NSCLC and a performance status of 3, who have not had previous systemic therapy, monotherapy with an EGFR tyrosine kinase inhibitor may be given, with the choice dependent on access and toxicity profile of each agent. ( IC , , L , W )
618
For patients with an activating EGFR mutation other than exon 20 insertion mutations, T790M, L858R or exon 19 deletion, (e.g., G719X, L861Q, S768I), and a performance status of 0–2, who have not had previous systemic therapy, clinicians may offer

Recommendation 1.7

afatinib monotherapy ( IC , , L , M )
618
or osimertinib ( IC , , L , W )
618
or standard treatment based on the ASCO/OH non-driver mutation guideline. ( IC , , L , M )
618

Recommendation 1.8

For patients with any activating EGFR mutation, regardless of PD-L1 expression levels (including exon 20 insertion mutations), single agent immunotherapy should not be used as first-line therapy. ( IC , , L , M )
618

Recommendation 1.9

For patients with an exon 20 insertion mutation causing resistance to first- and second-generation EGFR tyrosine kinase inhibitors, clinicians may offer platinum doublet chemotherapy with or without bevacizumab or standard treatment outlined in the ASCO/OH non-driver mutation guideline may be offered. ( IC , , L , M )
618

EGFR Second-line

Recommendation 2.1

For patients with a sensitizing (L858R/Ex19del) EGFR mutation with stage IV NSCLC and a performance status of 0-2 who have had previous EGFR targeted therapy (except osimertinib) and subsequently have an EGFR T790M resistance mutation, clinicians should recommend osimertinib. ( EB , B , H , S )
618

Recommendation 2.2

For patients with any EGFR mutation whose disease has progressed on EGFR tyrosine kinase inhibitors with no T790M mutation OR whose disease has progressed on osimertinib, clinicians may treat based on ASCO/OH non-driver mutation guideline. ( IC , , L , M )
618

ALK First-line

For patients with an ALK rearrangement, a PS of 0-2, and previously untreated NSCLC, clinicians should offer

Recommendation 3.1

alectinib or brigatinib ( EB , B , H , S )
618
or lorlatinib ( EB , B , L , W )
618

Recommendation 3.2

For patients with an ALK rearrangement, a PS of 0-2, and previously untreated NSCLC, if alectinib, brigatinib or lorlatinib are not available, clinicians should offer ceritinib or crizotinib. ( EB , B , H , S )
618

ALK Second-line

Recommendation 4.1

For patients with an ALK rearrangement, a performance status of 0–2, and have previously received alectinib or brigatinib, clinicians may offer lorlatinib. ( IC , , L , M )
618

Recommendation 4.2

For patients with an ALK rearrangement, a performance status of 0–2, and have previously received crizotinib in the first-line setting, clinicians should offer alectinib, brigatinib, or ceritinib in the second-line setting. ( EB , B , I , S )
618
For patients with an ALK rearrangement, a performance status of 0–2, and have received prior crizotinib in the first-line setting and either alectinib, brigatinib, or ceritinib in the second-line setting, clinicians may offer

Recommendation 4.3

lorlatinib ( IC , , L , M )
618
or clinicians may offer standard therapy based on the ASCO/OH non-driver mutation guideline in the third-line setting. ( IC , , L , W )
618

ROS1 First-line

Recommendation 5.1

For patients with ROS1 rearrangement, a performance status of 0–2, previously untreated NSCLC, clinicians may offer crizotinib or entrectinib. ( IC , , L , M )
618

Recommendation 5.2

For patients with ROS1 rearrangement, a performance status of 0–2, previously untreated NSCLC, clinicians may offer standard therapy based on the ASCO/OH non-driver mutation guideline. ( IC , , L , M )
618

Recommendation 5.3

For patients with ROS1 rearrangement, a performance status of 0–2, previously untreated NSCLC, clinicians may offer ceritinib or lorlatinib. ( IC , , L , W )
618

ROS1 Second-line

Recommendation 6.1

For patients with ROS1 rearrangement, a performance status of 0–2, previously treated with ROS1-targeted therapy, clinicians should offer standard therapy based on the ASCO/OH non-driver mutation guideline. ( IC , , L , M )
618

Recommendation 6.2

For patients with ROS1 rearrangement, a performance status of 0–2, previously treated with non-targeted therapy first-line, clinicians may offer crizotinib or entrectinib or ceritinib. ( IC , , L , M )
618

BRAF First-line

Recommendation 7.1

For patients with a BRAF V600E mutation, clinicians may offer dabrafenib/trametinib as first-line treatment. ( IC , , L , M )
618

Recommendation 7.2

For patients with a BRAF V600E mutation, clinicians may offer standard first-line therapy based on the ASCO/OH non-driver mutation guideline. ( IC , , L , M )
618

BRAF Second-line

Recommendation 8.1

For patients with a BRAF V600E mutation who have had previous BRAF/MEK (dabrafenib/trametinib) targeted therapy, clinicians should offer standard first-line therapy based on the ASCO/OH non-driver mutation guideline. ( IC , , L , M )
618
For patients with a BRAF V600E mutation, if BRAF-targeted therapy was not given in the first-line setting, clinicians may offer

Recommendation 8.2

dabrafenib/trametinib ( IC , , L , M )
618
or dabrafenib alone ( IC , , L , W )
618
or vemurafenib ( IC , B , L , W )
618

Recommendation 8.3

For patients with a BRAF V600E mutation who have had previous chemotherapy, immunotherapy, and/or BRAF-targeted therapy in the first- or subsequent-line setting, clinicians should offer standard treatment based on the ASCO/OH non-driver mutation guideline. ( IC , , L , M )
618

Recommendation 8.4

For patients with BRAF mutations other than BRAF V600E mutations, clinicians should offer standard therapy based on the ASCO/OH non-driver mutation guideline. ( IC , , L , M )
618

MET First-line

Recommendation 9.1

For patients with a MET exon 14 skipping mutation, a performance status of 0–2, previously untreated NSCLC, clinicians may offer MET-targeted therapy with capmatinib or tepotinib. ( IC , , L , M )
618

Recommendation 9.2

For patients with a MET exon 14 skipping mutation, a performance status of 0–2, previously untreated NSCLC, clinicians may offer standard first-line therapy based on the ASCO/OH non-driver mutations guideline. ( IC , , L , M )
618

MET Second-line

Recommendation 10.1

Patients with MET abnormalities other than exon 14 skipping mutations, a performance status of 0–2, or those previously treated with MET-targeted therapy, clinicians should offer standard therapy based on the ASCO/OH non-driver mutations guideline. ( IC , , L , M )
618

Recommendation 10.2

For patients with a MET exon 14 skipping mutation, a performance status of 0–2, who have previously received or been ineligible for first-line chemotherapy with or without immunotherapy, clinicians may offer MET-targeted therapy with capmatinib or tepotinib. ( IC , , L , M )
618

RET Rearrangement First-line

Recommendation 11.1

For patients with a RET rearrangement, a performance status of 0–2, and previously untreated NSCLC, clinicians may offer selpercatinib or pralsetinib. ( IC , , L , W )
618

Recommendation 11.2

For patients with a RET rearrangement, a performance status of 0–2, previously untreated NSCLC, clinicians may offer standard therapy based on the ASCO/OH non-driver mutation guideline ( IC , , L , M )
618

RET Rearrangement Second-line

Recommendation 12.1

For patients with RET rearrangement who have had previous RET-targeted therapy, clinicians may offer treatment per the non-driver mutation guideline. ( IC , , L , M )
618
For patients with RET rearrangement, if RET-targeted therapy was not given in the first-line setting, clinicians may offer

Recommendation 12.2

selpercatinib ( IC , , L , M )
618
or pralestinib ( IC , , L , W )
618

NTRK First-line

Recommendation 13.1

For patients with an NTRK fusion, a performance status of 0–2, previously untreated NSCLC, clinicians may offer entrectinib or larotrectinib. ( IC , , L , M )
618

Recommendation 13.2

For patients with an NTRK fusion, a performance status of 0–2, previously untreated NSCLC, clinicians may offer standard therapy based on the ASCO/OH non-driver mutation guideline ( IC , , L , M )
618

NTRK Second-line

Recommendation 14.1

For patients with an NTRK fusion, if NTRK-targeted therapy was not given in the first-line setting, clinicians may offer standard therapy based on the ASCO/OH non-driver mutation guideline. ( IC , , L , M )
618

Recommendation 14.2

For patients with an NTRK fusion previously treated NSCLC who have not received an NTRK inhibitor, clinicians may offer entrectinib or larotrectinib. ( IC , , L , M )
618

Recommendation Grading

Overview

Title

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

Authoring Organizations

Publication Month/Year

February 21, 2023

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Inclusion Criteria

Female, Male, Adult

Health Care Settings

Ambulatory, Home health, Hospital, Outpatient

Intended Users

Social worker, physician, nurse practitioner, nurse, physician assistant

Scope

Management, Treatment

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, Owen DH, Ismaila N, Blanchard E, Celano P, Florez N, Jain D, Singh N. Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2022.3. J Clin Oncol. 2023 Feb 21:JCO2202782. doi: 10.1200/JCO.22.02782. Epub ahead of print. PMID: 36802359.

Singh N, Temin S, Baker, Jr. S, et al. Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations Treatment: ASCO Guideline Update. J Clin Oncol. 2022 Jan 28. doi: 10.1200/JCO.22.00824

Hanna NH, et al. Therapy for Stage IV Non-Small Cell Lung Cancer with Driver Alterations: ASCO and OH (CCO) Joint Guideline Update. J Clin Oncol. 2021 Feb 16. doi: 10.1200/JCO.20.03570

The guideline was a cooperative effort among the American Society of Clinical Oncology and Ontario Health (Cancer Care Ontario).
 

Supplemental Methodology Resources

Data Supplement, Evidence Tables, Evidence Tables

Methodology

Number of Source Documents
152
Literature Search Start Date
December 1, 2015
Literature Search End Date
December 1, 2021