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

Updated: Jul 15, 2021
  • Author: Marvaretta M Stevenson, MD; Chief Editor: Nagla Abdel Karim, MD, PhD  more...
  • Print
Answer

Answer

Patients with metastatic (stage IV) or recurrent disease should undergo broad molecular testing to identify oncogenes or genetic alterations. Patients with actionable genetic alterations should be treated with corresponding targeted therapies; these are preferred over treatment with chemotherapy or immunotherapy.

EGFR mutations

Erlotinib, afatinib, osimertinib, 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 [83] 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). [84] Treatment recommendations include the following:

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

  • Osimertinib 80 mg PO once daily until disease progression or unacceptable toxicity [90]

EGFR exon 20 insertion–positive NSCLC detected by an FDA approved test, in who have progressed has progressed on or after platinum-based chemotherapy, treatment is with amivantamab. Dosage is based on baseline body weight.

Patients with baseline body weight < 80 kg:

  • Week 1: Day 1, 350 mg IV x 1 dose; Day 2, 700 mg IV x 1 dose
  • Weeks 2-4: 1050 mg IV weekly
  • After Week 4: 1050 mg IV q2Weeks
  • Continue until disease progression or unacceptable toxicity

Patients with baseline body weight ≥80 kg:

  • Week 1: Day 1, 350 mg IV x 1 dose; Day 2: 1050 mg IV x 1 dose
  • Weeks 2-4: 1400 mg IV weekly
  • After Week 4: 1400 mg IV q2Weeks
  • Continue until disease progression or unacceptable toxicity

 ROS-1 mutation positive NSCLC:

  • Crizotinib 250 mg PO q12h until disease progression or unacceptable toxicity [91]
  • Entrectinib 600 mg PO once daily until disease progression or unacceptable toxicity [92, 93]  

ALK-positive metastatic NSCLC:

  • Ceritinib 450mg PO once daily until disease progression or unacceptable toxicity [94]
  • Alectinib 600mg PO q12h until disease progression or unacceptable toxicity [95]
  • Lorlatinib 100 mg PO once daily until disease progression or unacceptable toxicity [96, 97]
  • crizotinib 250 mg po q12h unti disease progression or unacceptable toxicity  [98]
  • 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 [99]

BRAF V600E mutation-positive NSCLC:

MET exon 14 skipping mutation–positive NSCLC:

  • Capmatinib 400 mg PO BID; continue until disease progression or unacceptable toxicity [101]
  • Crizotinib 250 mg PO q12h until disease progression or unacceptable toxicity
  • Tepotinib 450 mg PO qDay until disease progression or unacceptable toxicity [102]

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 [103]  
  • Pralsetinib 400 mg PO qDay on an empty stomach; continue until disease progression or until unacceptable toxicity [104]

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

KRAS mutations 

KRAS G12C mutation–positive NSCLC: 

  • Sotorasib 960 mg PO daily until disease progression or unacceptable toxicity [81]  

Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!