What are the first-line treatment recommendations for 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

Patients with metastatic disease (stage IV) or recurrent disease after primary therapy (eg, surgery and/or radiation) should be considered for chemotherapy in order to improve quality of life, palliate symptoms, and improve overall survival. [11, 7] The goal is to treat for four to six cycles unless otherwise specified.

Chemotherapy regimens, including platinum-based doublets, are as follows:

  • Cisplatin 75 mg/m2 IV on day 1 plus  paclitaxel 175 mg/m2 IV on day 1 every 21 d [26] 27 or

  • Cisplatin 100 mg/m2 IV on day 1 plus  gemcitabine 1000 mg/m2 IV on days 1, 8, and 15 every 28 d [27]  or

  • Cisplatin 60 mg/m2 IV on day 1 plus  gemcitabine 1000 mg/m2 IV on days 1 and 8 every 21 d [28, 29]  or

  • Cisplatin 75 mg/m2 IV on day 1 plus  docetaxel 75 mg/m2 IV on day 1 every 21 d [8, 27]  or

  • Carboplatin AUC 6 IV on day 1 plus  paclitaxel 175-225 mg/m2 IV on day 1 every 21 d [27, 30]  or

  • Carboplatin AUC 6 IV on day 1 plus  paclitaxel 90 mg/m2 IV on days 1, 8, and 15 every 28 d [31, 32, 33]  or

  • Paclitaxel protein bound 100 mg/m2 IV on days 1, 8, and 15 of every 21 d plus carboplatin AUC 6 IV on day 1 [34]  or

  • Carboplatin AUC 6 IV on day 1 plus  docetaxel 75 mg/m2 IV on day 1 every 21 d [17]  or

  • Carboplatin AUC 5 IV on day 1 plus  gemcitabine 1250 mg/m2 IV on days 1 and 8 every 21 d [35, 36, 37]  or

  • Cisplatin 100 mg/m2 IV on day 1 every 28 d plus  vinorelbine 25 mg/m2 IV weekly [8] or

  • Cisplatin 40 mg/m2 IV on day 1 plus  vinorelbine 25 mg/m2 IV on days 1 and 8 every 21 d [28]  or

  • Carboplatin AUC 5 IV on day 1 plus  vinorelbine 30 mg/m2 IV on days 1 and 8 every 21 d [38]

Combination therapy for first-line treatment of metastatic NSCLC with PD-L1 tumor expression ≥1% is as follows [39] :

  • Nivolumab 3 mg/kg IV q2wk,  plus
  • Ipilimumab 1 mg/kg IV q6wk
  • Continue until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression

First-line treatment of metastatic squamous NSCLC is as follows:

  • Paclitaxel protein bound 100 mg/m2 IV on days 1, 8, and 15 of every 21 d plus carboplatin AUC 6 IV on day 1 [34]   or
  • Pembrolizumab 200 mg IV  and  carboplatin AUC 6 mg/mL/min on day 1 of each 21 d cycle for four cycles  plus  paclitaxel 200 mg/m 2 on day 1  or  nab-paclitaxel 100 mg/m 2 on days 1, 8, and 15 of each 21 d cycle for four cycles [40] ; alternative pembrolizumab dose is 400 mg q6wk  [41]

Bevacizumab-based regimens for patients who meet eligibility requirements (non-squamous histology, treated brain metastases, no history of hemoptysis) are as follows:

  • Carboplatin AUC 6 IV on day 1 plus  paclitaxel 200 mg/m2 IV on day 1 plus  bevacizumab 15 mg/kg IV on day 1 every 21 d (continue bevacizumab every 21 d after four to six cycles are completed; continue until disease progression) [42]  or

  • Cisplatin 80 mg/m2 IV on day 1 plus  gemcitabine 1250 mg/m2 IV on days 1 and 8 plus  bevacizumab 7.5-15 mg/kg IV on day 1 every 21 d (continue bevacizumab every 21 d after four to six cycles are completed); continue until disease progression or

  • Docetaxel 75 mg/m2 IV on day 1 plus  bevacizumab 15 mg/kg IV on day 1 every 21 d until disease progression or 52 wk of therapy [12] or

  • Carboplatin AUC 6 IV on day 1 plus  pemetrexed 500 mg/m2 IV on day 1 plus  bevacizumab 15 mg/kg IV on day 1 every 21 d, with pemetrexed and bevacizumab continued until disease progression (plus folate and vitamin B12 supplements, along with dexamethasone premedication for pemetrexed) [43]

Pemetrexed plus pembrolizumab plus platinum therapy for initial treatment in patients with nonsquamous NSCLC without EGFR or ALK genomic tumor aberrations are as follows: [44]

  • Pembrolizumab 200 mg plus  pemetrexed 500 mg/m2 plus  cisplatin 75 mg/m2 IV on day 1 every 21 d for four cycles (plus folate and vitamin B12 supplements along with dexamethasone premedication for pemetrexed) or

  • Pembrolizumab 200 mg plus  pemetrexed 500 mg/m2 plus carboplatin AUC 5 IV on day 1 every 21 d for four cycles (plus folate and vitamin B12 supplements along with dexamethasone premedication for pemetrexed)

  • Administer pemetrexed IV over 10 min after pembrolizumab and before platinum-based therapy

  • Alternative pembrolizumab dose is 400 mg IV q6wk

  • Following treatment with platinum-based therapy, continue pemetrexed with or without pembrolizumab until disease progression or unacceptable toxicity

Pemetrexed plus cisplatin for initial treatment in patients with nonsquamous NSCLC:

  • Pemetrexed 500 mg/m2 IV administered 10 minutes before cisplatin 75 mg/m2 IV on day 1 every 21 d for up to six cycles in the absence of disease progression or unacceptable toxicity

Treatment recommendations for tumors with epidermal growth factor receptor (EGFR) immunohistochemistry are as follows:

  • Cisplatin 80 mg/m2 IV on day 1 plus  vinorelbine 25 mg/m2 IV on days 1 and 8 plus cetuximab 400 mg/m2 IV loading dose, followed by 250 mg/m2 IV weekly every 21 d (continue cetuximab weekly after 4-6 cycles completed, until disease progression) [45, 46]

Treatment recommendations for tumors with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations are as follows: [47]

  • Ramucirumab 10 mg/kg IV q2wk  plus
  • Erlotinib 150 mg PO qd
  • Continue until disease progression or unacceptable toxicity

Treatment recommendations for anaplastic lymphoma kinase (ALK)–positive locally advanced or metastatic tumors are as follows:

  • Crizotinib 250 mg PO BID until disease progression; dosing interruption and/or dose reduction to 200 mg PO BID may be required, based on safety and tolerability; decrease to 250 mg PO daily if further reduction is needed [48]  OR

  • Ceritinib 750 mg PO daily until disease progression; dosing interruption and/or dose reduction may be required based on safety and tolerability [49]

  • Crizotinib resistance/intolerance: Alectinib 600 mg PO BID until disease progression; dosing interruption and/or dose reduction may be required based on safety and tolerability [50]

Pembrolizumab can be used as a single-agent first-line for tumors that express PD-L1 (Tumor Proportion Score [TPS] ≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, are as follows: [51, 52]

  • Pembrolizumab 200 mg IV q3wk or 400 mg IV q6wk until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression

Pembrolizumab is also indicated in combination with pemetrexed and carboplatin for first-line treatment of patients with metastatic nonsquamous NSCLC irrespective of PD-L1 expression as follows: [44]

  • Pembrolizumab 200 mg IV plus pemetrexed 500 mg/m 2 plus carboplatin (AUC 5 mg/mL/min) IV on Day 1 of each 21-day cycle for four cycles,  then pembrolizumab 200 mg IV q3wk until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression
  • Alternatively, pembrolizumab 400 mg IV q6wk plus pemetrexed 500 mg/m2 plus carboplatin (AUC 5 mg/mL/min) IV on Day 1 of each 21-day cycle for four cycles,  then pembrolizumab 400 mg IV q6wk until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression

Treatment recommendations for patients with contraindications to carboplatin or cisplatin are as follows:

  • Gemcitabine 1100 mg/m2 IV on days 1 and 8 plus docetaxel 100 mg/m2 IV on day 8 every 21 d [53, 54] or

  • Gemcitabine 1000-1200 mg/m2 IV on days 1 and 8 plus vinorelbine 25-30 mg/m2 IV on days 1 and 8 every 21 d [38, 55, 56, 57]


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