What are the second-line treatment recommendations for 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...
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Second-line therapy is given for advanced or recurrent disease after disease progression following first-line therapy. Second-line regimens are as follows:

  • Nivolumab 240 mg IV q2wk or 480 mg q4wk over 30 min; continue until disease progression or unacceptable toxicity [71]  or

  • Pembrolizumab 200 mg IV q3wk until disease progression or unacceptable toxicity (for up to 24 mo) in tumors that are programmed death ligand 1 (PD-L1) positive; patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab [68] ; alternative pembrolizumab dose is 400 mg IV q6wk or

  • Docetaxel 75 mg/m2 IV on day 1 every 21 d (goal, four to six cycles) [56, 59, 60, 57, 67] +/- ramucirumab 10 mg/kg IV [72]  or

  • Pemetrexed 500 mg/m2 IV on day 1 (non-squamous histology) every 21 d (goal, four to six cycles; include folate and vitamin B12 supplements along with dexamethasone premedication for pemetrexed) [67]  or

  • Erlotinib 150 mg PO daily for patients with EGFR mutation or gene amplification; given until disease progression [7, 33, 73, 74, 75, 76, 77, 78, 79]

  • Afatinib 40 mg PO daily for patients with metastatic squamous NSCLC that has progressed after platinum-based chemotherapy [80]  

  • Sotorasib 960 mg PO daily for KRAS G12C–mutated locally advanced or metastatic NSCLC in adults who have received at 1 prior systemic therapy; continue until disease progression or unacceptable toxicity [81]

  • A study by Herbst et al confirms that bevacizumab and erlotinib should not be used together for refractory or recurrent NSCLC at this time; erlotinib alone in second-line and third-line settings remains the standard of care. [82]

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