What are the single-agent therapy recommendations for specific genetic mutations in non-small cell lung cancer (NSCLC) stage IV or recurrent disease?

Updated: Mar 08, 2021
  • Author: Marvaretta M Stevenson, MD; Chief Editor: Nagla Abdel Karim, MD, PhD  more...
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Answer

Answer

EGFR mutations

Erlotinib, afatinib, and gefitinib are approved by the FDA for first-line treatment of metastatic NSCLC in patients whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations, as detected by an FDA-approved test, [7]  such as the cobas EGFR mutation test [85] and therascreen EGFR RGQ PCR Kit. Additionally, afatinib is indicated for first-line use in metastatic NSCLC for 3 additional nonresistant EGFR mutations (ie, L861Q, G719X, S768I). [86] Treatment recommendations include the following:

EGFR T790M mutation–positive NSCLC detected by an FDA approved test, in patients who have progressed on or after EGFR TKI therapy:

  • Osimertinib 80 mg PO once daily until disease progression or unacceptable toxicity [92]

Other mutations

ROS-1 mutation positive NSCLC:

  • Crizotinib 250 mg PO q12h until disease progression or unacceptable toxicity [93]
  • Entrectinib 600 mg PO once daily until disease progression or unacceptable toxicity [94, 95]  

ALK-positive metastatic NSCLC:

  • Ceritinib 450mg PO once daily until disease progression or unacceptable toxicity [96]
  • Alectinib 600mg PO q12h until disease progression or unacceptable toxicity [97]
  • Lorlatinib 100 mg PO once daily until disease progression or unacceptable toxicity [98, 99]

ALK-positive metastatic NSCLC in patient who have progressed on or are intolerant to crizotinib:

  • Brigatinib 90 mg PO once daily for the first 7 days; if 90 mg/day is tolerated, increase the dose to 180 mg PO until disease progression or unacceptable toxicity [100]

Disease progression during or following platinum-containing chemotherapy; patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving atezolizumab:

  • Atezolizumab 840 mg IV q2Weeks, 1200 mg IV q3wk or 1680 mg IV q4wk, until disease progression or unacceptable toxicity  [101, 102]

BRAF V600E mutation-positive NSCLC:

MET exon 14 skipping mutation–positive NSCLC:

  • Capmatinib 400 mg PO BID; continue until disease progression or unacceptable toxicity [104]
  • Crizotinib 250 mg PO q12h until disease progression or unacceptable toxicity
  • Tepotinib 450 mg PO qDay until disease progression or unacceptable toxicity [105]

RET fusion–positive NSCLC:

  • Selpercatinib 120 mg PO BID (weight < 50 kg) or 160 mg PO BID (weight 50 kg or greater); continue until disease progression or unacceptable toxicity [106]  
  • Pralsetinib 400 mg PO qDay on an empty stomach; continue until disease progression or until unacceptable toxicity [107]

NTRK mutation–positive NSCLC:

  • Larotrectinib 100 mg PO q12h until disease progression or unacceptable toxicity
  • Entrectinib 600 mg PO once daily until disease progression or unacceptable toxicity

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