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

Last updated April 12, 2023

Key Points

Key Points

  • In 2022, ASCO launched living clinical practice guidelines for systemic therapy for patients with stage IV non–small-cell lung cancer (NSCLC) with1 and without driver alterations.2 Based on new evidence from routine literature searches, this version of the stage IV non–small-cell lung cancer with driver alterations living guideline reviews evidence and provides updated recommendations on new therapeutics.
    1. Singh N, Temin S, Baker S, Jr., et al: Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline. J Clin Oncol:JCO2200824, 2022
    2. Singh N, Temin S, Baker S, Jr., et al: Therapy for Stage IV Non-Small-Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline. J Clin Oncol:JCO2200825, 2022
  • All patients with non-squamous NSCLC should have results of testing for potentially targetable mutations (alterations) prior to implementing therapy for advanced lung cancer, regardless of smoking status, when possible following other existing high quality testing guidelines.
  • This guideline includes recommendations regarding RET, MET, and NTRK alterations.
  • Chemotherapy is still an option at most stages.
  • This update (Recommendations 15.1 and 16.1) recommends the following for previously treated patients with HER2 or KRAS mutation:
    • Monotherapy treatment with trastuzumab deruxtecan may be offered to patients with advanced NSCLC and an activating HER2, ERBB2 mutation who have received prior systemic therapy.
    • Monotherapy treatment with sotorasib may be offered to patients with advanced NSCLC and a KRAS-G12C mutation who have received prior systemic therapy

Treatment

...Treatment...

...s otherwise listed, recommendations apply...


...EGFR Fi...

...ommendation 1.1For patients with a sensiti...

...1.2For patients with a sensitizing (L858...

...1.3For patients with a sensitizing (L...

...ation 1.4For patients with a sensitizing (L858R/e...

...n 1.5For patients with a sensitizing (L858R/...

...mendation 1.6For patients with a sensitizing (L...

...ecommendation 1....

...nib monotherapy ( IC , , L , M )618...

...rtinib ( IC , , L , W )618...

...tandard treatment based on the ASCO/OH non-...

...1.8For patients with any activating EGFR mu...

Recommendation 1.9For patients with an e...


...EGFR...

...ation 2.1For patients with a sensitizing...

...2.2For patients with any EGFR mutation whose...


...ALK Firs...

...ommendation 3...

...or brigatinib ( EB , B , H , S...

...latinib. ( EB , B , L ,...

....2For patients with an ALK rearrangement, a PS...


...ALK Second-line...

....1For patients with an ALK rearrangement, a...

...on 4.2For patients with an ALK rearrangement, a...

...ecommendation...

lorlatinib ( IC , , L ,...

...ay offer standard therapy based on th...


...ROS1 First-line...

...ndation 5.1For patients with ROS1 rearrangemen...

...ion 5.2For patients with ROS1 rearran...

...ecommendation 5.3For patients with ROS1 rearrange...


...ROS1 Second-line...

...on 6.1For patients with ROS1 rearrangement, a...

...ion 6.2For patients with ROS1 rearrangement...


...BRAF Firs...

...7.1For patients with a BRAF V600E...

...mendation 7.2For patients with a BRAF V600E...


...BRAF Second-line...

...mmendation 8.1For patients with a BRAF V600E...

...mmendation 8.2

...ametinib ( IC , , L , M )61...

...dabrafenib alone ( IC , , L...

...rafenib ( IC , B , L , W...

...dation 8.3For patients with a BRAF V600E mut...

...mmendation 8.4For patients with BRAF mutatio...


...MET First-...

...commendation 9.1For patients with a MET exon 14 s...

...9.2For patients with a MET exon 14 skipping m...


...endation 10.1Patients with MET abnormal...

...0.2For patients with a MET exon 14 skipping mu...


...RET Rear...

Recommendation 11.1For patients with a RET re...

...n 11.2For patients with a RET rearrangement, a p...


...RET Rearrangement...

...ommendation 12.1For patients with RET rearrangem...

...endation 12.2...

...percatinib ( IC , , L , M...

...alestinib. ( IC , , L , W...


...NTRK First-...

...ommendation 13.1For patients with an NT...

...dation 13.2For patients with an NTRK fusion,...


...NTRK Second-l...

...tion 14.1For patients with an NTRK fusion, if...

...endation 14.2For patients with an NTRK...


...New R...

...mmendation 15.1(Updated) For patients...

...ecommendation 16.1(Updated) For patients with adva...


...New Recommendati...

...16.2New: For patients with advanced NS...


...ary of Recommendations Recommendation #...


ASCO believes that cancer clinical trials are...