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

Publication Date: February 28, 2024

Key Points

Key Points

  • The treatment of advanced stage IV non-small-cell lung cancer (NSCLC) has evolved dramatically in the past decade.
  • The identification of actionable oncogenic driver alterations has allowed for the emergence of new, effective targeted treatments, that have resulted in significant survival gains.

Treatment

...atment

...uestion 1: What are the most effective fir...

...recommendations with multiple treatment opti...

...mal growth factor receptor (EG...

...etion, Exon 21 L858R substitution...

...inicians should offer osimertinib. ( EB ,...

...thers

...For other activating EGFR alterations, (G719...

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

...2.2. or standard treatment following th...

...ement: Recommendation 1.2, 1.2.1, and 1.2.2 ex...

...ny activating EGFR alteration, regard...

Exon 20 insertions

...ans may offer chemotherapy and amivantama...

...mivantamab is not available, clinicians s...

...lymphoma kinase (ALK)...

...should offer alectinib or brigatinib or lor...

.... If alectinib, brigatinib, or lorlatinib are not...

ROS1

...ns may offer crizotinib or entrectinib. ( EB , ,...

.... If crizotinib or entrectinib are not avail...

...FV600E

...ans may offer dabrafenib and trametinib, o...

...dabrafenib and trametinib, or encorafenib and b...

...n 14 skipping mutatio...

...nicians may offer capmatinib or tepotinib. (...

...If capmatinib or tepotinib is not available, clin...

...ET rearrangemen...

...icians should offer selpercatinib. ( EB , , H ,...

...If selpercatinib is not available, clinic...

...selpercatinib or pralsetinib are not...

...phic tyrosine receptor kinase (NTRK) rea...

...nicians may offer entrectinib or laro...

...8. If entrectinib or larotrectinib are not ava...

.... For patients with a poor performan...

...rehensive genomic biomarker test results sho...

...atement: PDL-1 IHC alone should not be u...

...ients with advanced lung cancer sh...


...linical Question 2: What are the most effe...

...Due to development of potentially targetable resi...

EGF...

...19 deletion, Exon 21 L858R subs...

...tients that develop EGFR T790M resistance alter...

2.2. For patients who have progres...

...ment: Anti-PD-(L)1 agents with platinum chemot...

...hers...

...patients with an exon 20 insertion alte...

AL...

...s who have previously received crizotinib, clini...

...ts who have previously received other ALK inh...

ROS...

...tients who have previously received crizotini...

...nicians should offer platinum-based chemotherapy...

...FV600E

...For patients who have not receive...

...s who have previously received BRAF or MEK targe...

2.10. For BRAF alterations other than BRAFV600...

...on 14 skipping mutation...

...patients who have not received MET-targeted...

...tients previously treated with MET-targeted...

...rearrangement

...13. For patients who have not recei...

...If selpercatinib or pralsetinib is not avai...

...rearrangemen...

...tients who have not received an NTRK inhibitor, cl...

....16. If entrectinib or larotrectin...

...dermal receptor factor 2 (HER...

...Clinicians may offer treatment with trastu...

...AS G12C...

....18. Clinicians may offer treatment with soto...

...Clinicians may offer treatment with ada...

...ing Statement: Note that adagrasib and...


Figure 1. Second-Line and Subsequent Treatment O...


...2. Treatment Options for Patients With Stage IV...


...t and Second Line Treatment Options...


...irst and Second Line Treatment Options for Patien...