Non-Small Cell Lung Cancer Treatment Regimens

Non-Small Cell Lung Cancer Treatment Regimens

Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment.

Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are provided only to supplement the latest treatment strategies.


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These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Note: All recommendations are category 2A unless otherwise indicated.

▶Targeted Therapy or Immunotherapy for Advanced or Metastatic Disease1

REGIMEN

DOSING

EGFR Exon 19 Deletion or L858R Mutations: First-Line Therapya-c

Preferred

Osimertinib (Category 1)2-6,d

Days 1-28: Osimertinib 80mg orally once daily.

Repeat cycle every 4 weeks.

Other Recommended

Afatinib (Category 1)7-9,d,e

Days 1-28: Afatinib 40mg orally once daily.

Repeat cycle every 4 weeks.

Dacomitinib (Category 1)10,11,d,e

Days 1-28: Dacomitinib 45mg orally once daily.

Repeat cycle every 4 weeks.

Erlotinib (Category 1)12-17,d

Days 1-28: Erlotinib 150mg orally once daily.

Repeat cycle every 4 weeks.

Erlotinibd + Bevacizumab12,18,19,f,g

Days 1-28: Erlotinib 150mg orally once daily

Repeat cycle every 4 weeks, with:

Day 1: Bevacizumab 15mg/kg IV

Repeat cycle every 3 weeks.

Erlotinibd + Ramucirumab12,20,21,h

Premedication is required.

Days 1-28: Erlotinib 150mg orally once daily

Repeat cycle every 4 weeks, with:

Day 1: Ramucirumab 10mg/kg IV over 60 minutes.

Repeat cycle every 2 weeks.

Gefitinib (Category 1)22-25,d

Days 1-28: Gefitinib 250mg orally once daily.

Repeat cycle every 4 weeks.

EGFR Exon 19 Deletion or L858R Mutations: Subsequent Therapya

If Progression on Osimertinibi

Osimertinib2-6,d

Days 1-28: Osimertinib 80mg orally once daily.

Repeat cycle every 4 weeks.

If further progression, refer to Systemic Therapy for Advanced or Metastatic Disease – Adenocarcinoma, Systemic Therapy for Advanced or Metastatic Disease – Squamous Cell Carcinoma

If Progression on Erlotinib (±Ramucirumab or Bevacizumab), Afatinib, Gefitinib, or Dacomitinibi

Afatinib (if T790M-)7-9,d,e

Days 1-28: Afatinib 40mg orally once daily.

Repeat cycle every 4 weeks.

Dacomitinib (if T790M-)10,11,d,e

Days 1-28: Dacomitinib 45mg orally once daily.

Repeat cycle every 4 weeks.

Erlotinib (if T790M-)12-17,d

Days 1-28: Erlotinib 150mg orally once daily.

Repeat cycle every 4 weeks.

Erlotinibd + Bevacizumab

(if T790M-)12,18,19,f,g

Days 1-28: Erlotinib 150mg orally once daily

Repeat cycle every 4 weeks, with:

Day 1: Bevacizumab 15mg/kg IV

Repeat cycle every 3 weeks.

Erlotinibd + Ramucirumab

(if T790M-)12,20,21,h

Premedication is required.

Days 1-28: Erlotinib 150mg orally once daily

Repeat cycle every 4 weeks, with:

Day 1: Ramucirumab 10mg/kg IV over 60 minutes.

Repeat cycle every 2 weeks.

Gefitinib (if T790M-)22-25,d

Days 1-28: Gefitinib 250mg orally once daily.

Repeat cycle every 4 weeks.

Osimertinib (if T790M+) (Category 1)2-6,d

Days 1-28: Osimertinib 80mg orally once daily.

Repeat cycle every 4 weeks.

If further progression, refer to Systemic Therapy for Advanced or Metastatic Disease – Adenocarcinoma, Systemic Therapy for Advanced or Metastatic Disease – Squamous Cell Carcinoma

EGFR S768I, L861Q, and/or G719X Mutation: First-Line Therapya,j

Preferred

Afatinib7-9,d,e

Days 1-28: Afatinib 40mg orally once daily.

Repeat cycle every 4 weeks.

Osimertinib2-6,d

Days 1-28: Osimertinib 80mg orally once daily.

Repeat cycle every 4 weeks.

Other Recommended

Dacomitinib10,11,d,e

Days 1-28: Dacomitinib 45mg orally once daily.

Repeat cycle every 4 weeks.

Erlotinib12-17,d

Days 1-28: Erlotinib 150mg orally once daily.

Repeat cycle every 4 weeks.

Gefitinib22-25,d

Days 1-28: Gefitinib 250mg orally once daily.

Repeat cycle every 4 weeks.

EGFR S768I, L861Q, and/or G719X Mutation: Subsequent Therapya,c

See EGFR Exon 19 Deletion or L858R Mutations: Subsequent Therapy

EGFR Exon 20 Insertion Mutation Positive: First-Line Therapya

Refer to Systemic Therapy for Advanced or Metastatic Disease – Subsequent

EGFR Exon 20 Insertion Mutation Positive: Subsequent Therapya

Amivantamab-vmjw26,27,k

Premedication is required.

If weight <80kg:

Day 1: Amivantamab-vmjw 350mg IV followed by:

Day 2: Amivantamab-vmjw 700mg IV followed by:

Days 8,15,22: Amivantamab-vmjw 1,050mg IV

Administer for one 4-week cycle followed by:

Days 1,15: Amivantamab-vmjw 1,050mg IV

Repeat cycle every 4 weeks. (beginning with Cycle 2).

OR

If weight ≥80kg:

Day 1: Amivantamab-vmjw 350mg IV followed by:

Day 2: Amivantamab-vmjw 1,050mg IV followed by:

Days 8,15,22: Amivantamab-vmjw 1,400mg IV

Administer for one 4-week cycle followed by:

Days 1,15: Amivantamab-vmjw 1,400mg IV

Repeat cycle every 4 weeks (beginning with Cycle 2).

Mobocertinib28,29,l

Days 1-28: Mobocertinib 160mg orally once daily.

Repeat cycle every 4 weeks.

If further progression, refer to Systemic Therapy for Advanced or Metastatic Disease – Adenocarcinoma, Systemic Therapy for Advanced or Metastatic Disease – Squamous Cell Carcinoma

KRAS G12C Mutation Positive: First-Line Therapya

Refer to Systemic Therapy for Advanced or Metastatic Disease – Adenocarcinoma, Systemic Therapy for Advanced or Metastatic Disease – Squamous Cell Carcinoma

KRAS G12C Mutation Positive: Subsequent Therapya

Sotorasib30,31

Days 1-28: Sotorasib 960mg orally once daily.

Repeat cycle every 4 weeks.

If further progression, refer to Systemic Therapy for Advanced or Metastatic Disease – Subsequent

ALK Rearrangement Positive: First-Line Therapya,m

Preferred

Alectinib (Category 1)32-35,n

Days 1-28: Alectinib 600mg orally twice daily.

Repeat cycle every 4 weeks.

Brigatinib (Category 1)36-38

Days 1-7: Brigatinib 90mg once daily, followed by:

Days 8-28: Brigatinib 180mg orally once daily

Administer for one 4-week cycle, followed by:

Days 1-28: Brigatinib 180mg orally once daily.

Repeat cycle every 4 weeks.

Lorlatinib (Category 1)39-42

Days 1-28: Lorlatinib 100mg orally once daily.

Repeat cycle every 4 weeks.

Other Recommended

Ceritinib (Category 1)43-47

Days 1-28: Ceritinib 450mg orally once daily.

Repeat cycle every 4 weeks.

Useful in Certain Circumstances

Crizotinib (Category 1)35,48-51

Days 1-28: Crizotinib 250mg orally twice daily.

Repeat cycle every 4 weeks.

ALK Rearrangement Positive: Subsequent Therapya

If Progression on Alectinib, Brigatinib, Ceritinib, or Lorlatinib

Alectinib32-35,n

Days 1-28: Alectinib 600mg orally twice daily.

Repeat cycle every 4 weeks.

Brigatinib36-38

Days 1-7: Brigatinib 90mg once daily, followed by:

Days 8-28: Brigatinib 180mg orally once daily

Administer for one 4-week cycle, followed by:

Days 1-28: Brigatinib 180mg orally once daily.

Repeat cycle every 4 weeks.

Ceritinib43-47

Days 1-28: Ceritinib 450mg orally once daily.

Repeat cycle every 4 weeks.

Lorlatinib (ALK G1202R)39-42

Days 1-28: Lorlatinib 100mg orally once daily.

Repeat cycle every 4 weeks.

If further progression, refer to Systemic Therapy for Advanced or Metastatic Disease – Adenocarcinoma, Systemic Therapy for Advanced or Metastatic Disease – Squamous Cell Carcinoma

If Progression on Crizotinib

Alectinib32-35,n

Days 1-28: Alectinib 600mg orally twice daily.

Repeat cycle every 4 weeks.

Brigatinib36-38

Days 1-7: Brigatinib 90mg once daily, followed by:

Days 8-28: Brigatinib 180mg orally once daily

Administer for one 4-week cycle, followed by:

Days 1-28: Brigatinib 180mg orally once daily.

Repeat cycle every 4 weeks.

Ceritinib43-47

Days 1-28: Ceritinib 450mg orally once daily.

Repeat cycle every 4 weeks.

Crizotinib35,48-51

Days 1-28: Crizotinib 250mg orally twice daily.

Repeat cycle every 4 weeks.

Lorlatinib39-42

Days 1-28: Lorlatinib 100mg orally once daily.

Repeat cycle every 4 weeks.

If further progression, refer to Systemic Therapy for Advanced or Metastatic Disease – Adenocarcinoma, Systemic Therapy for Advanced or Metastatic Disease – Squamous Cell Carcinoma

ROS1 Rearrangement Positive: First-Line Therapya,o

Preferred

Crizotinib35,48-51

Days 1-28: Crizotinib 250mg orally twice daily.

Repeat cycle every 4 weeks.

Entrectinib52-54

Days 1-28: Entrectinib 600mg orally once daily.

Repeat cycle every 4 weeks.

Other Recommended

Ceritinib43-47

Days 1-28: Ceritinib 450mg orally once daily.

Repeat cycle every 4 weeks.

ROS1 Rearrangement Positive: Subsequent Therapya

If progression on Entrectinib, Crizotinib, or Ceritinib

Ceritinib43-47

Days 1-28: Ceritinib 450mg orally once daily.

Repeat cycle every 4 weeks.

Crizotinib35,48-51

Days 1-28: Crizotinib 250mg orally twice daily.

Repeat cycle every 4 weeks.

Entrectinib52-54

Days 1-28: Entrectinib 600mg orally once daily.

Repeat cycle every 4 weeks.

Lorlatinib39-42

Days 1-28: Lorlatinib 100mg orally once daily.

Repeat cycle every 4 weeks.

If further progression, refer to Systemic Therapy for Advanced or Metastatic Disease – Adenocarcinoma, Systemic Therapy for Advanced or Metastatic Disease – Squamous Cell Carcinoma

BRAF V600E Mutation Positive: First-Line Therapya,p

Preferred

Dabrafenibq + Trametinib55-58

Days 1-28: Dabrafenib 150mg orally twice daily

Days 1-28: Trametinib 2mg orally once daily.

Repeat cycle every 4 weeks.

Useful in Certain Circumstances

Dabrafenib55,59,60,q

Days 1-28: Dabrafenib 150mg orally twice daily.

Repeat cycle every 4 weeks.

Vemurafenib59,61,62

Days 1-28: Vemurafenib 960mg orally twice daily.

Repeat cycle every 4 weeks.

Refer to Systemic Therapy for Advanced or Metastatic Disease – Adenocarcinoma, Systemic Therapy for Advanced or Metastatic Disease – Squamous Cell Carcinoma

BRAF V600E Mutation Positive: Subsequent Therapya

Dabrafenibq + Trametinib55-58

Days 1-28: Dabrafenib 150mg orally twice daily

Days 1-28: Trametinib 2mg orally once daily.

Repeat cycle every 4 weeks.

If further progression, refer to Systemic Therapy for Advanced or Metastatic Disease – Adenocarcinoma, Systemic Therapy for Advanced or Metastatic Disease – Squamous Cell Carcinoma or Systemic Therapy for Advanced or Metastatic Disease – Subsequent

NTRK1/2/3 Gene Fusion Positive: First-Line Therapy/Subsequent Therapya,r

Preferred Therapy

Entrectinib52-54

Days 1-28: Entrectinib 600mg orally once daily.

Repeat cycle every 4 weeks.

Larotrectinib63,64

Days 1-28: Larotrectinib 100mg orally twice daily.

Repeat cycle every 4 weeks.

Useful in Certain Circumstances

Refer to Systemic Therapy for Advanced or Metastatic Disease – Adenocarcinoma, Systemic Therapy for Advanced or Metastatic Disease – Squamous Cell Carcinoma or Systemic Therapy for Advanced or Metastatic Disease – Subsequent

MET Exon 14 Skipping Mutation: First-Line Therapy/Subsequent Therapya,s

Preferred

Capmatinib65,66

Days 1-28: Capmatinib 400mg orally twice daily.

Repeat cycle every 4 weeks.

Tepotinib67,68

Days 1-28: Tepotinib 450mg orally once daily.

Repeat cycle every 4 weeks.

Useful in Certain Circumstances

Crizotinib35,48-51

Days 1-28: Crizotinib 250mg orally twice daily.

Repeat cycle every 4 weeks.

Refer to Systemic Therapy for Advanced or Metastatic Disease – Adenocarcinoma, Systemic Therapy for Advanced or Metastatic Disease – Squamous Cell Carcinoma or Systemic Therapy for Advanced or Metastatic Disease – Subsequent

RET Rearrangement Positive: First-line Therapy/Subsequent Therapya,t

Preferred

Pralsetinib69,70

Days 1-28: Pralsetinib 400mg orally once daily.

Repeat cycle every 4 weeks.

Selpercatinib71,72

If weight <50kg:

Days 1-28: Selpercatinib 120mg orally twice daily.

Repeat cycle every 4 weeks.

OR

If weight ≥50kg:

Days 1-28: Selpercatinib 160mg orally twice daily.

Repeat cycle every 4 weeks.

Useful in Certain Circumstances

Cabozantinib73-75

Days 1-28: Cabozantinib 60mg orally once daily.

Repeat cycle every 4 weeks.

Other Recommended

Refer to Systemic Therapy for Advanced or Metastatic Disease – Adenocarcinoma, Systemic Therapy for Advanced or Metastatic Disease – Squamous Cell Carcinoma or Systemic Therapy for Advanced or Metastatic Disease – Subsequent

PD-L1 Positive (≥50%) and Negative for Actionable Molecular Biomarkers, with No Contraindications to PD-1 or PD-L1 Inhibitors (PS 0-2): Adenocarcinoma, Large Cell, NSCLC NOS First-line Therapy

Preferred

Atezolizumab (Category 1)76-80,u

Day 1: Atezolizumab 840mg IV.

Repeat cycle every 2 weeks.

OR

Day 1: Atezolizumab 1,200mg IV.

Repeat cycle every 3 weeks.

OR

Day 1: Atezolizumab 1,680mg IV.

Repeat cycle every 4 weeks.

Carboplatin + Pemetrexed + Pembrolizumab (Category 1)81-84,u,v

Premedication is required.

Day 1: Pembrolizumab 200mg IV over 30 minutes, followed by:

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes, followed by:

Day 1: Carboplatin AUC 5 IV over 30 minutes.

Repeat every 3 weeks for 4-6 cycles, followed by maintenance therapy with:

Day 1: Pembrolizumab 200mg IV over 30 minutes OR

Day 1: Pembrolizumab 400mg IV over 30 minutes every other cycle, followed by maintenance therapy with:

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes.

Repeat cycle every 3 weeks for 2 years, followed by:

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes.

Repeat cycle every 3 weeks.

Cisplatin + Pemetrexed + Pembrolizumab (Category 1)81,82,84,u,v,dd

Premedication is required.

Day 1: Pembrolizumab 200mg IV over 30 minutes, followed by:

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes, followed by:

Day 1: Cisplatin 75mg/m2 IV over 2 hours.

Repeat cycle every 3 weeks for 4-6 cycles, followed by maintenance therapy with:

Day 1: Pembrolizumab 200mg IV over 30 minutes OR

Day 1: Pembrolizumab 400mg IV over 30 minutes every other cycle, followed by maintenance therapy with:

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes.

Repeat cycle every 3 weeks for 2 years, followed by:

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes.

Repeat cycle every 3 weeks.

Cemiplimab-rwlc (Category 1)85,86,u

Day 1: Cemiplimab-rwlc 350mg IV over 30 minutes

Repeat cycle every 3 weeks.

Pembrolizumab (Category 1)81,84,87-89,u

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks for up to 2 years of therapy.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 6 weeks for up to 2 years of therapy.

Other Recommended

Carboplatin + Albumin-Bound Paclitaxel + Atezolizumab76,90,u

Day 1: Atezolizumab 1,200mg IV, followed by:

Days 1,8,15: Albumin-Bound Paclitaxel 100mg/m2 IV over 30 minutes

Day 1: Carboplatin AUC 6 IV over 30 minutes

Repeat cycle every 3 weeks for 4-6 cycles, followed by maintenance therapy with:

Day 1: Atezolizumab 840mg IV

Repeat cycle every 2 weeks.

OR

Day 1: Atezolizumab 1,200mg IV, followed by:

Days 1,8,15: Albumin-Bound Paclitaxel 100mg/m2 IV over 30 minutes

Day 1: Carboplatin AUC 6 IV over 30 minutes

Repeat cycle every 3 weeks for 4-6 cycles, followed by maintenance therapy with:

Day 1: Atezolizumab 1,200mg IV

Repeat cycle every 3 weeks.

OR

Day 1: Atezolizumab 1,200mg IV, followed by:

Days 1,8,15: Albumin-Bound Paclitaxel 100mg/m2 IV over 30 minutes

Day 1: Carboplatin AUC 6 IV over 30 minutes

Repeat cycle every 3 weeks for 4-6 cycles, followed by maintenance therapy with:

Day 1: Atezolizumab 1,680mg IV

Repeat cycle every 4 weeks.

Carboplatin + Paclitaxel + Bevacizumab + Atezolizumab (Category 1)18,76,91,f,g,u,w

Premedication is required.

Day 1: Atezolizumab 1,200mg IV followed by:

Day 1: Bevacizumab 15mg/kg IV followed by:

Day 1: Paclitaxel 200mg/m2 IV over 3 hours

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

OR

Day 1: Atezolizumab 1,200mg IV, followed by:

Day 1: Bevacizumab 15mg/kg IV, followed by:

Day 1: Paclitaxel 175mg/m2 (for Asian patients) over 3 hours

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Nivolumab + Ipilimumab + Pemetrexed + Carboplatin (Category 1)92,93,94,u,v

Premedication is required.

Days 1,22: Nivolumab 360mg IV over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes, followed by:

Days 1,22: Pemetrexed 500mg/m2 IV over 10 minutes

Days 1,22: Carboplatin AUC 6 IV over 30 minutes.

Administer for one 6-week cycle, followed by maintenance therapy with:

Days 1,22: Nivolumab 360mg IV over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 6 weeks for a maximum of 2 years.

Nivolumab + Ipilimumab + Pemetrexed + Cisplatin (Category 1)92,93,94,u,v,dd

Premedication is required.

Days 1,22: Nivolumab 360mg IV over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes, followed by:

Days 1,22: Pemetrexed 500mg/m2 IV over 10 minutes

Days 1,22: Cisplatin 75mg/m2 IV over 2 hours.

Administer for one 6-week cycle, followed by maintenance therapy with:

Days 1,22: Nivolumab 360mg IV over 30 minutes, followed by maintenance therapy with:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 6 weeks for a maximum of 2 years.

Useful in Certain Circumstances

Nivolumab + Ipilimumab (Category 1)92,93,95,u

Days 1, 15,29: Nivolumab 3mg/kg over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 6 weeks for a maximum of 2 years.

PD-L1 Positive (≥50%) and Negative for Actionable Molecular Biomarkers, with No Contraindications to PD-1 or PD-L1 Inhibitors (PS 0-2): Adenocarcinoma, Large Cell, NSCLC NOS Continuation Maintenance Therapy

Atezolizumab76-80,u,x

Day 1: Atezolizumab 840mg IV.

Repeat cycle every 2 weeks.

OR

Day 1: Atezolizumab 1,200mg IV.

Repeat cycle every 3 weeks.

OR

Day 1: Atezolizumab 1,680mg IV.

Repeat cycle every 4 weeks.

Atezolizumab + Bevacizumab (Category 1)18,76,91,u,y

Day 1: Atezolizumab 1,200mg IV

Day 1: Bevacizumab 15mg/kg IV.

Repeat cycle every 3 weeks.

Cemiplimab-rwlc (Category 1)85,86,u

Day 1: Cemiplimab-rwlc 350mg IV over 30 minutes

Repeat cycle every 3 weeks.

Nivolumab + Ipilimumab (Category 1)92,93,95,u,ee

Days 1, 15,29: Nivolumab 3mg/kg over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 6 weeks for a maximum of 2 years.

Pembrolizumab (Category 1)81,84,87-89,u,z

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks for up to 2 years of therapy.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 6 weeks for up to 2 years of therapy.

Pembrolizumab + Pemetrexed (Category 1)81-84,u,v,aa

Premedication is required.

Day 1: Pembrolizumab 200mg IV over 30 minutes, followed by:

Day 1: Pembrolizumab 200mg over 30 minutes

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes every other cycle, followed by:

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes.

Repeat cycle every 3 weeks until 2 years of therapy has been completed, followed by:

Day 1: Pemetrexed 500mg/m2 IV.

Repeat cycle every 3 weeks.

For Progressive Diseasebb

Refer to Systemic Therapy for Advanced or Metastatic Disease – Adenocarcinoma, Systemic Therapy for Advanced or Metastatic Disease – Subsequent

PD-L1 Positive (≥50%) and Negative for Actionable Molecular Biomarkers, with No Contraindications to PD-1 or PD-L1 Inhibitors (PS 0-2): Squamous Cell Carcinoma First-line Therapy

Preferred

Atezolizumab (Category 1)76-80,u

Day 1: Atezolizumab 840mg IV.

Repeat cycle every 2 weeks.

OR

Day 1: Atezolizumab 1,200mg IV.

Repeat cycle every 3 weeks.

OR

Day 1: Atezolizumab 1,680mg IV.

Repeat cycle every 4 weeks.

Carboplatin + Albumin-Bound Paclitaxel + Pembrolizumab (Category 1)81,84,96,u,w

Premedication is required.

Day 1: Pembrolizumab 200mg IV over 30 minutes, followed by:

Days 1,8,15: Albumin-bound Paclitaxel 100mg/m2 over 30 minutes

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat every 3 weeks for 4 cycles, followed by:

Day 1: Pembrolizumab 200mg IV over 30 minutes

Repeat cycle every 3 weeks for 24 months.

OR

Day 1: Pembrolizumab 200mg IV over 30 minutes, followed by:

Days 1,8,15: Albumin-bound Paclitaxel 100mg/m2 over 30 minutes

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 3 weeks for 4 cycles, followed by maintenance therapy with:

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 6 weeks for 2 years.

Carboplatin + Paclitaxel + Pembrolizumab (Category 1)81,84,96,91,u,w

Premedication is required.

Day 1: Pembrolizumab 200mg IV over 30 minutes, followed by:

Day 1: Paclitaxel 200mg/m2 IV over 3 hours

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat every 3 weeks for 4 cycles, followed by maintenance therapy with:

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Maintenance: Repeat cycle every 3 weeks for 2 years.

OR

Day 1: Pembrolizumab 200mg IV over 30 minutes, followed by:

Day 1: Paclitaxel 200mg/m2 IV over 3 hours

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat every 3 weeks for 4 cycles, followed by maintenance therapy with:

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Maintenance: Repeat cycle every 6 weeks for 24 months.

Cemiplimab-rwlc (Category 1)85,86,u

Day 1: Cemiplimab-rwlc 350mg IV over 30 minutes

Repeat cycle every 3 weeks.

Pembrolizumab (Category 1)81,84,87-89,u

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks for up to 2 years of therapy.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 6 weeks for up to 2 years of therapy.

Other Recommended

Nivolumab + Ipilimumab + Paclitaxel + Carboplatin (Category 1)92-94,u,w

Premedication is required.

Days 1,22: Nivolumab 360mg IV over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes, followed by:

Days 1,22: Paclitaxel 200mg/m2 IV over 3 hours, followed by:

Days 1,22: Carboplatin AUC 6 IV over 30 minutes.

Administer for one 6-week cycle, followed by maintenance therapy with:

Days 1,22: Nivolumab 360mg IV, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 6 weeks for a maximum of 2 years.

Useful in Certain Circumstances

Nivolumab + Ipilimumab (Category 1)92,93,95,u

Days 1,15,29: Nivolumab 3mg/kg over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 6 weeks for a maximum of 2 years.

PD-L1 Positive (≥50%) and Negative for Actionable Molecular Biomarkers, with No Contraindications to PD-1 or PD-L1 Inhibitors (PS 0-2): Squamous Cell Carcinoma Continuation Maintenance Therapy

Atezolizumab76-80,u,x

Day 1: Atezolizumab 840mg IV.

Repeat cycle every 2 weeks.

OR

Day 1: Atezolizumab 1,200mg IV.

Repeat cycle every 3 weeks.

OR

Day 1: Atezolizumab 1,680mg IV.

Repeat cycle every 4 weeks.

Cemiplimab-rwlc (Category 1)85,86,u

Day 1: Cemiplimab-rwlc 350mg IV over 30 minutes

Repeat cycle every 3 weeks.

Nivolumab + Ipilimumab (Category 1)92,93,95,u,ee

Days 1, 15, 29: Nivolumab 3mg/kg over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 6 weeks for a maximum of 2 years.

Pembrolizumab (Category 1)81,84,87-89,u,z,cc

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks for up to 2 years of therapy.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 6 weeks for up to 2 years of therapy.

For Progressive Diseasebb

Refer to Systemic Options for Advanced or Metastatic Disease: Adenocarcinoma, Systemic Therapy for Advanced or Metastatic Disease – Subsequent: Adenocarcinoma or Squamous Cell Carcinoma

PD-L1 Positive (≥1-49%) and Negative for Actionable Molecular Biomarkers, with No Contraindications to PD-1 or PD-L1 Inhibitors (PS 0-2): Adenocarcinoma, Large Cell, NSCLC NOS First-Line Therapy

Preferred

Carboplatin + Pemetrexed + Pembrolizumab (Category 1)81-84,u,w

Premedication is required.

Day 1: Pembrolizumab 200mg IV over 30 minutes, followed by:

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes, followed by:

Day 1: Carboplatin AUC 5 IV over 30 minutes.

Repeat every 3 weeks for 4-6 cycles, followed by maintenance therapy with:

Day 1: Pembrolizumab 200mg IV over 30 minutes OR

Day 1: Pembrolizumab 400mg IV over 30 minutes every other cycle, followed by maintenance therapy with:

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes.

Repeat cycle every 3 weeks for 2 years, followed by:

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes.

Repeat cycle every 3 weeks.

Cisplatin + Pemetrexed + Pembrolizumab (Category 1)81,82,84,u,v,dd

Premedication is required.

Day 1: Pembrolizumab 200mg IV over 30 minutes, followed by:

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes, followed by:

Day 1: Cisplatin 75mg/m2 IV over 2 hours .

Repeat cycle every 3 weeks for 4-6 cycles, followed by maintenance therapy with:

Day 1: Pembrolizumab 200mg IV over 30 minutes OR

Day 1: Pembrolizumab 400mg IV over 30 minutes every other cycle, followed by:

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes.

Repeat cycle every 3 weeks for 2 years, followed by:

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes.

Repeat cycle every 3 weeks.

Other Recommended

Carboplatin + Albumin-Bound Paclitaxel + Atezolizumab76,90,u

Premedication is required.

Day 1: Atezolizumab 1,200mg IV, followed by:

Days 1,8,15: Albumin-Bound Paclitaxel 100mg/m2 IV over 30 minutes

Day 1: Carboplatin AUC 6 IV over 30 minutes

Repeat cycle every 3 weeks for 4-6 cycles, followed by maintenance therapy with:

Day 1: Atezolizumab 840mg IV.

Repeat cycle every 2 weeks.

OR

Day 1: Atezolizumab 1,200mg IV, followed by:

Days 1,8,15: Albumin-Bound Paclitaxel 100mg/m2 IV over 30 minutes

Day 1: Carboplatin AUC 6 IV over 30 minutes

Repeat cycle every 3 weeks for 4-6 cycles, followed by maintenance therapy with:

Day 1: Atezolizumab 1,200mg IV.

Repeat cycle every 3 weeks.

OR

Day 1: Atezolizumab 1,200mg IV, followed by:

Days 1,8,15: Albumin-Bound Paclitaxel 100mg/m2 IV over 30 minutes

Day 1: Carboplatin AUC 6 IV over 30 minutes

Repeat cycle every 3 weeks for 4-6 cycles, followed by maintenance therapy with:

Day 1: Atezolizumab 1,680mg IV.

Repeat cycle every 4 weeks.

Carboplatin + Paclitaxel + Bevacizumab + Atezolizumab

(Category 1)18,91,f,g,u,w

Premedication is required.

Day 1: Atezolizumab 1,200mg IV followed by:

Day 1: Bevacizumab 15mg/kg IV followed by:

Day 1: Paclitaxel 200mg/m2 IV over 3 hours

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

OR

Day 1: Atezolizumab 1,200mg IV, followed by:

Day 1: Bevacizumab 15mg/kg IV, followed by:

Day 1: Paclitaxel 175mg/m2 (for Asian patients) over 3 hours

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Nivolumab + Ipilimumab + Pemetrexed + Carboplatin (Category 1)92-94,u,v

Premedication is required.

Days 1,22: Nivolumab 360mg IV over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes, followed by:

Days 1,22: Pemetrexed 500mg/m2 IV over 10 minutes, followed by:

Days 1,22: Carboplatin AUC 6 IV over 30 minutes.

Administer for one 6-week cycle, followed by maintenance therapy with:

Days 1,22: Nivolumab 360mg IV over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 6 weeks for a maximum of 2 years.

Nivolumab + Ipilimumab + Pemetrexed + Cisplatin (Category 1)92,93,95,u,v,dd

Premedication is required.

Days 1,22: Nivolumab 360mg IV over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes, followed by:

Days 1,22: Pemetrexed 500mg/m2 IV over 10 minutes

Days 1,22: Cisplatin 75mg/m2 IV over 2 hours.

Administer for one 6-week cycle, followed by maintenance therapy with:

Days 1,22: Nivolumab 360mg IV over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 6 weeks for a maximum of 2 years.

Useful in Certain Circumstances

Nivolumab + Ipilimumab (Category 1)92,93,95,u

Days 1,15,29: Nivolumab 3mg/kg over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 6 weeks for a maximum of 2 years.

Pembrolizumab (Category 2B)81,84,87-89,u

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks for up to 2 years of therapy.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 6 weeks for up to 2 years of therapy.

PD-L1 Positive (≥1-49%) and Negative for Actionable Molecular Biomarkers, with No Contraindications to PD-1 or PD-L1 Inhibitors (PS 0-2): Adenocarcinoma, Large Cell, NSCLC NOS Continuation Maintenance Therapy

Atezolizumab76-80,u,x

Day 1: Atezolizumab 840mg IV.

Repeat cycle every 2 weeks.

OR

Day 1: Atezolizumab 1,200mg IV.

Repeat cycle every 3 weeks.

OR

Day 1: Atezolizumab 1,680mg IV.

Repeat cycle every 4 weeks.

Atezolizumab + Bevacizumab (Category 1)18,76,91,f,g,u,y

Day 1: Atezolizumab 1,200mg IV

Day 1: Bevacizumab 15mg/kg IV.

Repeat cycle every 3 weeks.

Nivolumab + Ipilimumab (Category 1)92-95,u,ee

Days 1,15,29: Nivolumab 3mg/kg over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 6 weeks for a maximum of 2 years.

Pembrolizumab (Category 2B)81,84,87-89,u,z

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks for up to 2 years of therapy.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 6 weeks for up to 2 years of therapy.

Pembrolizumab + Pemetrexed (Category 1)81-84,u,v,aa

Premedication is required.

Day 1: Pembrolizumab 200mg IV over 30 minutes OR

Day 1: Pembrolizumab 400mg IV over 30 minutes every other cycle, followed by:

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes.

Repeat cycle every 3 weeks until 2 years of therapy has been completed, followed by:

Day 1: Pemetrexed 500mg/m2 IV.

Repeat cycle every 3 weeks.

For Progressive Diseasebb

See Systemic Options for Advanced or Metastatic Disease: Adenocarcinoma, Systemic Therapy for Advanced or Metastatic Disease – Subsequent: Adenocarcinoma or Squamous Cell Carcinoma

PD-L1 Positive (≥1-49%) and Negative for Actionable Molecular Biomarkers, with No Contraindications to PD-1 or PD-L1 Inhibitors (PS 0-2): Squamous Cell Carcinoma First-Line Therapy

Preferred

Carboplatin + Albumin-Bound Paclitaxel + Pembrolizumab (Category 1)81,84,96,u

Day 1: Pembrolizumab 200mg IV over 30 minutes, followed by:

Days 1,8,15: Albumin-bound Paclitaxel 100mg/m2 over 30 minutes

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat every 3 weeks for 4 cycles, followed by maintenance therapy with:

Day 1: Pembrolizumab 200mg IV over 30 minutes

Repeat cycle every 3 weeks for 2 years.

OR

Day 1: Pembrolizumab 200mg IV over 30 minutes, followed by:

Days 1,8,15: Albumin-bound Paclitaxel 100mg/m2 over 30 minutes

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 3 weeks for 4 cycles, followed by maintenance therapy with:

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 6 weeks for 2 years.

Carboplatin + Paclitaxel + Pembrolizumab (Category 1)81,84,96,u,w

Premedication is required.

Day 1: Pembrolizumab 200mg IV over 30 minutes, followed by:

Day 1: Paclitaxel 200mg/m2 IV over 3 hours

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat every 3 weeks for 4 cycles, followed by maintenance therapy with:

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Maintenance: Repeat cycle every 3 weeks for 2 years.

OR

Day 1: Pembrolizumab 200mg IV over 30 minutes, followed by:

Day 1: Paclitaxel 200mg/m2 IV over 3 hours

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat every 3 weeks for 4 cycles, followed by maintenance therapy with:

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Maintenance: Repeat cycle every 6 weeks for 2 years.

Other Recommended

Nivolumab + Ipilimumab + Paclitaxel + Carboplatin

(Category 1)92-94,u,w

Premedication is required.

Days 1,22: Nivolumab 360mg IV over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes, followed by:

Days 1,22: Paclitaxel 200mg/m2 IV over 3 hours, followed by:

Days 1,22: Carboplatin AUC 6 IV over 30 minutes.

Administer for one 6-week cycle, followed by continuation maintenance with:

Days 1,22: Nivolumab 360mg IV, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 6 weeks for a maximum of 2 years.

Useful in Certain Circumstances

Nivolumab + Ipilimumab (Category 1)92-95,u

Days 1,15,29: Nivolumab 3mg/kg over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 6 weeks for a maximum of 2 years.

Pembrolizumab (Category 2B)81,84,87-89,u

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks for up to 2 years of therapy.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 6 weeks for up to 2 years of therapy.

PD-L1 Positive (≥1-49%) and Negative for Actionable Molecular Biomarkers, with No Contraindications to PD-1 or PD-L1 Inhibitors (PS 0-2): Squamous Cell Carcinoma Continuation Maintenance Therapy

Nivolumab + Ipilimumab (Category 1)92-95,u,ee

Days 1,15,29: Nivolumab 3mg/kg over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 6 weeks for a maximum of 2 years.

Pembrolizumab81,84,87-89,u,z,cc

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks for up to 2 years of therapy.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 6 weeks for up to 2 years of therapy.

For Progressive Diseasebb

See Systemic Options for Advanced or Metastatic Disease: Adenocarcinoma, Systemic Therapy for Advanced or Metastatic Disease – Subsequent: Adenocarcinoma or Squamous Cell Carcinoma

PD-L1 Positive (<1%) and Negative for Actionable Molecular Biomarker (PS 0-2): Initial Systemic Therapy

See Systemic Therapy for Advanced or Metastatic Disease

PD-L1 Positive (<1%) and Negative for Actionable Molecular Biomarker (PS 0-2): Subsequent Therapy

See Systemic Therapy for Advanced or Metastatic Disease – Maintenance, Systemic Therapy for Advanced or Metastatic Disease – Subsequent or Progression: Adenocarcinoma or Squamous Cell Carcinoma

PD-L1 Positive (<1%) and Negative for Actionable Molecular Biomarker (PS 3-4): Initial Systemic/Subsequent Therapy

Best supportive care.

▶Systemic Therapy for Advanced or Metastatic Disease

Adenocarcinoma, Large Cell, NSCLC NOS (PS 0-1)

No contraindications to PD-1 or PD-L1 Inhibitors

Preferred

Pembrolizumab + Carboplatin + Pemetrexed (Category 1)81-84,u,v

Premedication is required.

Day 1: Pembrolizumab 200mg IV over 30 minutes, followed by:

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes, followed by:

Day 1: Carboplatin AUC 5 IV over 30 minutes.

Repeat every 3 weeks for 4-6 cycles, followed by maintenance therapy with:

Day 1: Pembrolizumab 200mg IV over 30 minutes OR

Day 1: Pembrolizumab 400mg IV over 30 minutes every other cycle, followed by:

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes.

Repeat cycle every 3 weeks for 2 years, followed by:

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes.

Repeat cycle every 3 weeks.

Pembrolizumab + Cisplatin + Pemetrexed (Category 1)81,82,84,u,v,dd

Premedication is required.

Day 1: Pembrolizumab 200mg IV over 30 minutes, followed by:

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes, followed by:

Day 1: Cisplatin 75mg/m2 IV over 2 hours.

Repeat cycle every 3 weeks for 4-6 cycles, followed by maintenance therapy with:

Day 1: Pembrolizumab 200mg IV over 30 minutes OR

Day 1: Pembrolizumab 400mg IV over 30 minutes every other cycle, followed by:

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes.

Repeat cycle every 3 weeks for 2 years, followed by:

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes.

Repeat cycle every 3 weeks.

Other Recommended

Atezolizumab + Carboplatin + Albumin-bound Paclitaxel76,90,u

Day 1: Atezolizumab 1,200mg IV, followed by:

Days 1,8,15: Albumin-Bound Paclitaxel 100mg/m2 IV over 30 minutes

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles, followed by maintenance therapy with:

Day 1: Atezolizumab 840mg IV.

Repeat cycle every 2 weeks.

OR

Day 1: Atezolizumab 1,200mg IV, followed by:

Days 1,8,15: Albumin-Bound Paclitaxel 100mg/m2 IV over 30 minutes

Day 1: Carboplatin AUC 6 IV over 30 minutes

Repeat cycle every 3 weeks for 4-6 cycles, followed by maintenance therapy with:

Day 1: Atezolizumab 1,200mg IV.

Repeat cycle every 3 weeks.

OR

Day 1: Atezolizumab 1,200mg IV, followed by:

Days 1,8,15: Albumin-Bound Paclitaxel 100mg/m2 IV over 30 minutes

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles, followed by maintenance therapy with:

Day 1: Atezolizumab 1,680mg IV.

Repeat cycle every 4 weeks.

Atezolizumab + Carboplatin + Paclitaxel + Bevacizumab (Category 1)18,91,f,g,u,w

Premedication is required.

Day 1: Atezolizumab 1,200mg IV followed by:

Day 1: Bevacizumab 15mg/kg IV followed by:

Day 1: Paclitaxel 200mg/m2 IV over 3 hours

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

OR

Day 1: Atezolizumab 1,200mg IV, followed by:

Day 1: Bevacizumab 15mg/kg IV, followed by:

Day 1: Paclitaxel 175mg/m2 (for Asian patients) over 3 hours

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Nivolumab + Ipilimumab92,93,95,u

Days 1, 15, 29: Nivolumab 3mg/kg over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 6 weeks for a maximum of 2 years.

Nivolumab + Ipilimumab + Pemetrexed + Carboplatin (Category 1)92-94,u,v

Premedication is required.

Days 1,22: Nivolumab 360mg IV over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes, followed by:

Days 1,22: Pemetrexed 500mg/m2 IV over 10 minutes, followed by:

Days 1,22: Carboplatin AUC 6 IV over 30 minutes.

Administer for one 6-week cycle, followed by continuation maintenance with:

Days 1,22: Nivolumab 360mg IV over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 6 weeks for a maximum of 2 years.

Nivolumab + Ipilimumab + Pemetrexed + Cisplatin (Category 1)92,93,94u,v,dd

Premedication is required.

Days 1,22: Nivolumab 360mg IV over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes, followed by:

Days 1,22: Pemetrexed 500mg/m2 IV over 10 minutes, followed by:

Days 1,22: Cisplatin 75mg/m2 IV over 2 hours.

Administer for one 6-week cycle, followed by continuation maintenance with:

Days 1,22: Nivolumab 360mg IV over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 6 weeks for a maximum of 2 years.

Contraindications to PD-1 or PD-L1 Inhibitors

Useful in Certain Circumstances

Bevacizumab + Carboplatin + Paclitaxel (Category 1)18,81,97,f,g,w,gg

Premedication is required.

Day 1: Paclitaxel 200mg/m2 IV over 3 hours followed by:

Day 1: Carboplatin AUC 6 IV over 30 minutes

Day 1: Bevacizumab 15mg/kg IV.

Repeat cycle every 3 weeks for 6 cycles.

Bevacizumab + Carboplatin + Pemetrexed18,98,f,g,v,gg

Premedication is required.

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes, followed by:

Day 1: Carboplatin AUC 6 IV over 30 minutes

Day 1: Bevacizumab 15mg/kg IV.

Repeat cycle every 3 weeks for 4-6 cycles.

Bevacizumab + Cisplatin + Pemetrexed18,99,f,g,v,dd,gg

Premedication is required.

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes, followed by:

Day 1: Cisplatin 75mg/m2 IV over 2 hours

Day 1: Bevacizumab 7.5mg/kg IV.

Repeat cycle every 3 weeks for 4-6 cycles.

Carboplatin + Albumin-bound Paclitaxel (Category 1)100

Days 1,8,15: Albumin-bound Paclitaxel 100mg/m2 IV over 30 minutes

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Carboplatin + Docetaxel (Category 1)101,hh

Premedication is required.

Day 1: Docetaxel 75mg/m2 IV over 60 minutes, followed by:

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Carboplatin + Etoposide

(Category 1)102,103

Day 1: Carboplatin AUC 5 IV over 30 minutes

Days 1-3: Etoposide 100mg/m2 IV over 60 minutes daily.

Repeat cycle every 3 weeks for 4-6 cycles.

Carboplatin + Gemcitabine (Category 1)104

Days 1,8,15: Gemcitabine 1,000mg/m2 IV over 30 minutes

Day 1: Carboplatin AUC 5 IV over 30 minutes.

Repeat cycle every 4 weeks for 4-6 cycles.

Carboplatin + Paclitaxel (Category 1)105,106,w

Premedication is required.

Day 1: Paclitaxel 200mg/m2 IV over 3 hours, followed by:

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Carboplatin + Pemetrexed (Category 1)107,v

Premedication is required.

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes, followed by:

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Cisplatin + Docetaxel

(Category 1)101,dd,hh

Premedication is required.

Day 1: Docetaxel 75mg/m2 IV over 60 minutes, followed by:

Day 1: Cisplatin 75mg/m2 IV over 2 hours.

Repeat cycle every 3 weeks for 4-6 cycles.

Cisplatin + Etoposide

(Category 1)108,dd

Day 1: Cisplatin 100mg/m2 IV over 2 hours

Days 1-3: Etoposide 100mg/m2 IV over 60 minutes daily.

Repeat cycle every 3 weeks for 4-6 cycles.

Cisplatin + Gemcitabine

(Category 1)110-112,dd

Days 1,8: Gemcitabine 1,000-1,250mg/m2 IV over 30 minutes, followed by:

Day 1: Cisplatin 75-80mg/m2 IV over 2 hours.

Repeat cycle every 3 weeks for 4-6 cycles.

Cisplatin + Paclitaxel

(Category 1)113,w,dd

Premedication is required.

Day 1: Paclitaxel 135mg/m2 IV over 3 hours, followed by:

Day 1: Cisplatin 75mg/m2 IV over 2 hours.

Repeat cycle every 3 weeks for 4-6 cycles.

Cisplatin + Pemetrexed

(Category 1)111,114,v,dd

Premedication is required.

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes, followed by:

Day 1: Cisplatin 75mg/m2 IV over 2 hours.

Repeat cycle every 3 weeks for 4-6 cycles.

Gemcitabine + Docetaxel (Category 1)115,hh

Premedication is required.

Days 1,8: Gemcitabine 1,000-1,250mg/m2 IV over 30 minutes

Day 8: Docetaxel 85mg/m2 IV over 60 minutes, followed by:

Day 8: Gemcitabine 1000mg/m2 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Gemcitabine + Vinorelbine (Category 1)116

Days 1,8: Vinorelbine 25mg/m2 IV over 5-10 minutes

Days 1,8: Gemcitabine 1,000mg/m2 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Adenocarcinoma, Large Cell, NSCLC NOS (PS 2)

Preferred

Carboplatin + Pemetrexed107,v

Premedication is required.

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes, followed by:

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Other Recommended

Carboplatin + Albumin-Bound Paclitaxel100

Days 1,8,15: Albumin-bound Paclitaxel 100mg/m2 IV over 30 minutes

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Carboplatin + Docetaxel101,hh

Premedication is required.

Day 1: Docetaxel 75mg/m2 IV over 60 minutes, followed by:

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Carboplatin + Etoposide102,103

Day 1: Carboplatin AUC 5 IV over 30 minutes

Days 1-3: Etoposide 100mg/m2 IV over 60 minutes daily.

Repeat cycle every 3 weeks for 4-6 cycles.

Carboplatin + Gemcitabine104

Days 1,8,15: Gemcitabine 1,000mg/m2 IV over 30 minutes

Day 1: Carboplatin AUC 5 IV over 30 minutes.

Repeat cycle every 4 weeks for 4-6 cycles.

Carboplatin + Paclitaxel105,106,w

Premedication is required.

Day 1: Paclitaxel 200mg/m2 IV over 3 hours, followed by:

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Useful in Certain Circumstances

Albumin-Bound Paclitaxel117,118

Day 1: Albumin-bound Paclitaxel 260mg/m2 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

OR

Days 1,8,15: Albumin-bound Paclitaxel 125mg/m2 IV over 30 minutes.

Repeat cycle every 4 weeks for 4-6 cycles.

Docetaxel119,120,hh

Premedication is required.

Day 1: Docetaxel 75mg/m2 IV over 60 minutes.

Repeat cycle every 3 weeks for 4-6 cycles

Gemcitabine112,121,122

Days 1,8,15: Gemcitabine 1,000-1,250mg/m2 IV over 30 minutes.

Repeat cycle every 4 weeks for 4-6 cycles.

OR

Days 1 and 8: Gemcitabine 1,250mg/m2 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Gemcitabine + Docetaxel115,hh

Premedication is required.

Day 1: Gemcitabine 1,000mg/m2 IV over 30 minutes

Day 8: Docetaxel 85mg/m2 IV over 60 minutes, followed by:

Day 8: Gemcitabine 1,000mg/m2 IV over 30 minutes.

Repeat every 3 weeks for 4-6 weeks.

Gemcitabine + Vinorelbine116

Days 1,8: Vinorelbine 25mg/m2 IV over 5-10 minutes

Days 1,8: Gemcitabine 1,000mg/m2 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Paclitaxel123-125,w

Premedication is required.

Day 1: Paclitaxel 200-225mg/m2 IV over 3 hours.

Repeat cycle every 3 weeks for 4-6 cycles.

OR

Days 1,8,15: Paclitaxel 80mg/m2 IV over 60 minutes.

Repeat cycle every 4 weeks for 4-6 cycles.

Pemetrexed126-128,v

Premedication is required.

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Adenocarcinoma, Large Cell, NSCLC NOS (PS 2)

Best supportive care.

Squamous Cell Carcinoma (PS 0-1) – No contraindications to PD-1 or PD-L1 Inhibitorsll

Preferred

Pembrolizumab + Carboplatin + Paclitaxel (Category 1)81,84,96,u,w

Premedication is required.

Day 1: Pembrolizumab 200mg IV over 30 minutes, followed by:

Day 1: Paclitaxel 200mg/m2 IV over 3 hours

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat every 3 weeks for 4 cycles, followed by maintenance therapy with:

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Maintenance: Repeat cycle every 3 weeks for 2 years.

OR

Day 1: Pembrolizumab 200mg IV over 30 minutes, followed by:

Day 1: Paclitaxel 200mg/m2 IV over 3 hours

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat every 3 weeks for 4 cycles, followed by maintenance therapy with:

Day 1: Pembrolizumab 400 IV over 30 minutes.

Maintenance: Repeat cycle every 6 weeks for 2 years.

Pembrolizumab + Carboplatin + Albumin-Bound Paclitaxel (Category 1)81,84,96,u

Day 1: Pembrolizumab 200mg IV over 30 minutes, followed by:

Days 1,8,15: Albumin-bound Paclitaxel 100mg/m2 over 30 minutes

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat every 3 weeks for 4 cycles, followed by maintenance therapy with:

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks for up to 2 years.

OR

Day 1: Pembrolizumab 200mg IV over 30 minutes, followed by:

Days 1,8,15: Albumin-bound Paclitaxel 100mg/m2 over 30 minutes

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 3 weeks for 4 cycles, followed by maintenance therapy with:

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 6 weeks for up to 2 years.

Other Recommended

Nivolumab + Ipilimumab92,93,95,u

Days 1,15,29: Nivolumab 3mg/kg over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 6 weeks for a maximum of 2 years.

Nivolumab + Ipilimumab + Paclitaxel + Carboplatin

(Category 1)92-94,u,w

Premedication is required.

Days 1,22: Nivolumab 360mg IV over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes, followed by:

Days 1,22: Paclitaxel 200mg/m2 IV over 3 hours, followed by:

Days 1,22: Carboplatin AUC 6 IV over 30 minutes.

Administer for one 6-week cycle, followed by:

Days 1,22: Nivolumab 360mg IV, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 6 weeks for a maximum of 2 years.

Useful in Certain Circumstances – Contraindications to PD-1 or PD-L1 Inhibitorsll

Carboplatin + Albumin-Bound Paclitaxel (Category 1)100

Days 1,8,15: Albumin-bound Paclitaxel 100mg/m2 IV over 30 minutes

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Carboplatin + Docetaxel (Category 1)101,hh

Premedication is required.

Day 1: Docetaxel 75mg/m2 IV over 60 minutes, followed by:

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Carboplatin + Gemcitabine (Category 1)104

Days 1,8,15: Gemcitabine 1,000mg/m2 IV over 30 minutes

Day 1: Carboplatin AUC 5 IV over 30 minutes.

Repeat cycle every 4 weeks for 4-6 cycles.

Carboplatin + Paclitaxel (Category 1)105,106,w

Premedication is required.

Day 1: Paclitaxel 200mg/m2 IV over 3 hours, followed by:

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 3 weeks for 4 cycles.

Cisplatin + Docetaxel

(Category 1)101,dd,hh

Premedication is required.

Day 1: Docetaxel 75mg/m2 IV over 60 minutes, followed by:

Day 1: Cisplatin 75mg/m2 IV over 2 hours.

Repeat cycle every 3 weeks for 4-6 cycles.

Cisplatin + Etoposide

(Category 1)108,dd

Day 1: Cisplatin 100mg/m2 IV over 2 hours

Days 1-3: Etoposide 100mg/m2 IV over 60 minutes daily.

Repeat cycle every 3 weeks for 4-6 cycles.

Cisplatin + Gemcitabine (Category 1)110-112,dd

Days 1 and 8: Gemcitabine 1,000-1,250mg/m2 IV over 30 minutes, followed by:

Day 1: Cisplatin 75-80mg/m2 IV over 2 hours.

Repeat cycle every 3 weeks for 4-6 cycles.

Cisplatin + Paclitaxel

(Category 1)113,w,dd

Premedication is required.

Day 1: Paclitaxel 135mg/m2 IV over 3 hours, followed by:

Day 1: Cisplatin 75mg/m2 IV over 2 hours.

Repeat cycle every 3 weeks for 4-6 cycles.

Gemcitabine + Docetaxel (Category 1)115,hh

Premedication is required.

Days 1 and 8: Gemcitabine 1,000-1,250mg/m2 IV over 30 minutes

Day 8: Docetaxel 85mg/m2 IV over 60 minutes, followed by:

Day 8: Gemcitabine 1000mg/m2 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Gemcitabine + Vinorelbine (Category 1)116

Days 1 and 8: Vinorelbine 25mg/m2 IV over 5-10 minutes

Days 1 and 8: Gemcitabine 1,000mg/m2 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Squamous Cell Carcinoma (PS 2)

Preferred

Carboplatin + Albumin-Bound Paclitaxel100

Days 1,8,15: Albumin-bound Paclitaxel 100mg/m2 IV over 30 minutes

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Carboplatin + Gemcitabine104

Days 1,8,15: Gemcitabine 1,000mg/m2 IV over 30 minutes

Day 1: Carboplatin AUC 5 IV over 30 minutes.

Repeat cycle every 4 weeks for 4-6 cycles.

Carboplatin + Paclitaxel105,106,w

Premedication is required.

Day 1: Paclitaxel 200mg/m2 IV over 3 hours, followed by:

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 3 weeks for 4 cycles.

Other Recommended

Carboplatin + Docetaxel101,hh

Premedication is required.

Day 1: Docetaxel 75mg/m2 IV over 60 minutes, followed by:

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Carboplatin + Etoposide102,103

Day 1: Carboplatin AUC 5 IV over 30 minutes

Days 1-3: Etoposide 100mg/m2 IV over 60 minutes daily.

Repeat cycle every 3 weeks for 4-6 cycles.

Useful in Certain Circumstances

Albumin-Bound Paclitaxel117,118

Day 1: Albumin-bound Paclitaxel 260mg/m2 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

OR

Days 1,8,15: Albumin-bound Paclitaxel 125mg/m2 IV over 30 minutes.

Repeat cycle every 4 weeks for 4-6 cycles.

Docetaxel119,120,hh

Premedication is required.

Day 1: Docetaxel 75mg/m2 IV over 60 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Gemcitabine112,121,122

Days 1,8,15: Gemcitabine 1,000-1,250mg/m2 IV over 30 minutes.

Repeat cycle every 4 weeks for 4-6 cycles.

OR

Days 1,8: Gemcitabine 1,250mg/m2 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Gemcitabine + Docetaxel115,hh

Premedication is required.

Day 1: Gemcitabine 1,000mg/m2 IV over 30 minutes

Day 8: Docetaxel 85mg/m2 IV over 60 minutes, followed by:

Day 8: Gemcitabine 1,000mg/m2 IV over 30 minutes.

Repeat every 3 weeks for 4-6 weeks.

Gemcitabine + Vinorelbine116

Days 1,8: Vinorelbine 25mg/m2 IV over 5-10 minutes

Days 1,8: Gemcitabine 1,000mg/m2 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Paclitaxel123-125,w

Premedication is required.

Day 1: Paclitaxel 200-225mg/m2 IV over 3 hours.

Repeat cycle every 3 weeks for 4-6 cycles.

OR

Days 1,8,15: Paclitaxel 80mg/m2 IV over 60 minutes.

Repeat cycle every 4 weeks for 4-6 cycles.

Squamous cell Carcinoma (PS 3-4)

Best supportive care.

▶Systemic Therapy for Advanced or Metastatic Disease — Maintenance

Adenocarcinoma, Large Cell, NSCLC NOS (PS 0-2)

Continuation Maintenance

Atezolizumab76-80,u,x

Day 1: Atezolizumab 840mg IV.

Repeat cycle every 2 weeks.

OR

Day 1: Atezolizumab 1,200mg IV.

Repeat cycle every 3 weeks.

OR

Day 1: Atezolizumab 1,680mg IV.

Repeat cycle every 4 weeks.

Atezolizumabp-s + Bevacizumab (Category 1)18,76,91,f,g,u,y

Day 1: Atezolizumab 1,200mg IV

Day 1: Bevacizumab 15mg/kg IV.

Repeat cycle every 3 weeks.

Bevacizumab (Category 1)18,97,f,g

Day 1: Bevacizumab 15mg/kg IV.

Repeat cycle every 3 weeks.

Bevacizumab + Pemetrexed18,98,99,f,g,v,ii

Premedication is required.

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes

Day 1: Bevacizumab 7.5-15mg/kg IV.

Repeat cycle every 3 weeks.

Gemcitabine

(Category 2B)112,121,122

Days 1,8,15: Gemcitabine 1,000-1,250mg/m2 IV over 30 minutes.

Repeat cycle every 4 weeks for 4-6 cycles.

OR

Days 1 and 8: Gemcitabine 1,250mg/m2 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Nivolumabp-s + Ipilimumab92,93,95,u,ee

Days 1,15,29: Nivolumab 3mg/kg over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 6 weeks for a maximum of 2 years.

Pembrolizumab + Pemetrexed (Category 1)91u,v,aa

Premedication is required.

Day 1: Pembrolizumab 200mg IV over 30 minutes OR

Day 1: Pembrolizumab 400mg IV over 30 minutes every other cycle, followed by:

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes.

Repeat cycle every 3 weeks until 2 years of therapy has been completed, followed by:

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes.

Repeat cycle every 3 weeks.

Pemetrexed (Category 1)126-128,v

Premedication is required.

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes.

Repeat every 3 weeks.

Switch Maintenance

Pemetrexed126-128,v

Premedication is required.

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes.

Repeat every 3 weeks.

Squamous Cell Carcinoma (PS 0-2)

Continuation Maintenance

Gemcitabine (Category 2B)112,121,122

Days 1,8,15: Gemcitabine 1,000-1,250mg/m2 IV over 30 minutes.

Repeat cycle every 4 weeks for 4-6 cycles.

OR

Days 1,8: Gemcitabine 1,250mg/m2 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Nivolumab + Ipilimumab92,93,95,u,ee

Days 1, 15,29: Nivolumab 3mg/kg over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 6 weeks for a maximum of 2 years.

Pembrolizumab81,84,87-89,u,cc

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks for up to 2 years of therapy.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 6 weeks for up to 2 years of therapy.

Adenocarcinoma, Large Cell, NSCLC NOS, Squamous Cell Carcinoma (PS 3-4)

Best Supportive Care

▶Systemic Therapy for Advanced or Metastatic Disease — Subsequent

Adenocarcinoma, Large Cell, NSCLC NOS (PS 0-2)

Preferred (No previous immunotherapy)ff

Atezolizumab (Category 1)76,77-80,u

Day 1: Atezolizumab 840mg IV.

Repeat cycle every 2 weeks.

OR

Day 1: Atezolizumab 1,200mg IV.

Repeat cycle every 3 weeks.

OR

Day 1: Atezolizumab 1,680mg IV.

Repeat cycle every 4 weeks.

Nivolumab (Category 1)92,129-132,u

Day 1: Nivolumab 240mg IV over 30 minutes

Repeat every 2 weeks.

OR

Day 1: Nivolumab 480mg IV over 30 minutes

Repeat every 4 weeks.

Pembrolizumab (Category 1)81,84,87-89,u

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks for up to 2 years of therapy.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 6 weeks for up to 2 years of therapy.

Other Recommended (No previous immunotherapy or previous immunotherapy)ff

Albumin-bound Paclitaxel117,118

Day 1: Albumin-bound Paclitaxel 260mg/m2 IV over 30 minutes.

Repeat cycle every 3 weeks.

OR

Days 1,8,15: Albumin-bound Paclitaxel 125mg/m2 IV over 30 minutes.

Repeat cycle every 4 weeks.

Docetaxel119,120,hh

Premedication is required.

Day 1: Docetaxel 75mg/m2 IV over 60 minutes.

Repeat cycle every 3 weeks.

Gemcitabine112,121,122

Premedication is required.

Days 1,8,15: Gemcitabine 1,000-1,250mg/m2 IV over 30 minutes.

Repeat cycle every 4 weeks.

OR

Days 1 and 8: Gemcitabine 1,250mg/m2 IV over 30 minutes.

Repeat cycle every 3 weeks.

Pemetrexed126-128,v

Premedication is required.

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes.

Repeat cycle every 3 weeks.

Ramucirumab + Docetaxel133,h,hh

Premedication is required.

Day 1: Ramucirumab 10mg/kg IV over 60 minutes, followed by:

Day 1: Docetaxel 75mg/m2 IV over 60 minutes.

Repeat cycle every 3 weeks.

Squamous Cell Carcinoma (PS 0-2)

Preferred (No previous immunotherapy)ff

Atezolizumab (Category 1)76-80,u

Day 1: Atezolizumab 840mg IV.

Repeat cycle every 2 weeks.

OR

Day 1: Atezolizumab 1,200mg IV.

Repeat cycle every 3 weeks.

OR

Day 1: Atezolizumab 1,680mg IV.

Repeat cycle every 4 weeks.

Nivolumab (Category 1)92,129-132,u

Day 1: Nivolumab 240mg IV over 30 minutes

Repeat every 2 weeks.

OR

Day 1: Nivolumab 480mg IV over 30 minutes

Repeat every 4 weeks.

Pembrolizumab (Category 1)81,84,87-89,u

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks for up to 2 years of therapy.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 6 weeks for up to 2 years of therapy.

Other Recommended (No previous immunotherapy or previous immunotherapy)ff

Albumin-bound Paclitaxel117,118

Day 1: Albumin-bound Paclitaxel 260mg/m2 IV over 30 minutes.

Repeat cycle every 3 weeks.

OR

Days 1,8,15: Albumin-bound Paclitaxel 125mg/m2 IV over 30 minutes.

Repeat cycle every 4 weeks.

Docetaxel119,120,hh

Premedication is required.

Day 1: Docetaxel 75mg/m2 IV over 60 minutes.

Repeat cycle every 3 weeks.

Gemcitabine112,121,122

Days 1,8,15: Gemcitabine 1,000-1,250mg/m2 IV over 30 minutes.

Repeat cycle every 4 weeks for 4-6 cycles.

OR

Days 1 and 8: Gemcitabine 1,250mg/m2 IV over 30 minutes.

Repeat cycle every 3 weeks.

Ramucirumab + Docetaxel133,h,hh

Premedication is required.

Day 1: Ramucirumab 10mg/kg IV over 60 minutes, followed by:

Day 1: Docetaxel 75mg/m2 IV over 60 minutes.

Repeat cycle every 3 weeks.

Adenocarcinoma, Large Cell, NSCLC NOS, Squamous Cell Carcinoma (PS 3-4)

Best supportive care.

▶Systemic Therapy for Advanced or Metastatic Disease — Progressionbb,ff

Adenocarcinoma, Large Cell, NSCLC NOSmm,zz

 • PS 0-2:Nivolumab, Pembrolizumab, or Atezolizumab, Docetaxel (Category 2B), Pemetrexed (Category 2B), Gemcitabine (Category 2B), Ramucirumab + Docetaxel (Category 2B), or Albumin-bound Paclitaxel (Category 2B)

 • PS 3-4: Best supportive care

 • Options for further progression are best supportive care or clinical trial

Squamous Cell Carcinomamm,zz

 • PS 0-2: Nivolumab, Pembrolizumab, or Atezolizumab, Docetaxel (Category 2B), Gemcitabine (Category 2B), Ramucirumab + Docetaxel (Category 2B), or Albumin-bound Paclitaxel (Category 2B)

 • PS 3-4: Best supportive care

 • Options for further progression are best supportive care or clinical trial.

▶Systemic Therapy Regimens for Neoadjuvant and Adjuvant Therapy

Preferred (Nonsquamous)

Cisplatin + Pemetrexed111,114,v,dd

Premedication is required.

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes followed by:

Day 1: Cisplatin 75mg/m2 IV over 2 hours.

Repeat cycle every 3 weeks for 4 cycles.

Preferred (Squamous)

Cisplatin + Docetaxel101,dd,hh

Premedication is required.

Day 1: Docetaxel 75mg/m2 IV over 60 minutes, followed by:

Day 1: Cisplatin 75mg/m2 over 2 hours.

Repeat cycle every 3 weeks for 4 cycles.

Cisplatin + Gemcitabine111,112,dd

Days 1,8: Gemcitabine 1,250mg/m2 IV over 30 minutes, followed by:

Day 1: Cisplatin 75mg/m2 IV over 2 hours.

Repeat cycle every 3 weeks for 4 cycles.

Other Recommended Regimens

Cisplatin + Etoposide109,dd

Day 1: Cisplatin 100mg/m2 IV over 2 hours

Days 1-3: Etoposide 100mg/m2 IV over 60 minutes.

Repeat cycle every 4 weeks for 4 cycles.

Cisplatin + Vinorelbine109,134,dd

Day 1: Cisplatin 75-80mg/m2 IV over 2 hours

Days 1,8: Vinorelbine 25-30mg/m2 IV over 5-10 minutes.

Repeat cycle every 3 weeks for 4 cycles.

OR

Days 1,8: Cisplatin 50mg/m2 IV over 60 minutes

Days 1,8,15,22: Vinorelbine 25mg/m2 IV over 5-10 minutes.

Repeat cycle every 4 weeks for 4 cycles.

OR

Day 1: Cisplatin 100mg/m2 over 2 hours

Days 1,8,15,22: Vinorelbine 30mg/m2 IV over 5-10 minutes.

Repeat cycle every 4 weeks for 4 cycles.

Useful in Certain Circumstances

Chemotherapy Regimens for Patients with Comorbidities or Patients Not Able to Tolerate Cisplatin

Carboplatin + Gemcitabine135

Days 1,8: Gemcitabine 1,000mg/m2 IV over 30 minutes

Day 1: Carboplatin AUC 5 IV over 30 minutes.

Repeat cycle every 3 weeks for 4 cycles.

Carboplatin + Paclitaxel105,106,w

Premedication is required.

Day 1: Paclitaxel 200mg/m2 IV over 3 hours, followed by:

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 3 weeks for 4 cycles.

Carboplatin + Pemetrexed (non-squamous)136,v

Premedication is required.

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes

Day 1: Carboplatin AUC 5 IV over 30 minutes.

Repeat cycle every 3 weeks for 4 cycles.

All regimens can be used for sequential chemotherapy/RT

Adjuvant Systemic Therapy

Atezolizumab76,137,u

Day 1: Atezolizumab 840mg IV.

Repeat cycle every 2 weeks for 1 year.

OR

Day 1: Atezolizumab 1,200mg IV.

Repeat cycle every 3 weeks for 1 year.

OR

Day 1: Atezolizumab 1,680mg IV.

Repeat cycle every 4 weeks for 1 year.

Adjuvant Systemic Therapy

Osimertinib (for patients with completely resected Stage IB-IIIA [exon 19 deletion or L858R] who received previous adjuvant chemotherapy or who are ineligible to receive platinum- based chemotherapy)2-6,d,jj

Days 1-28: Osimertinib 80mg orally once daily.

Repeat cycle every 4 weeks for 3 years.

Neoadjuvant Systemic Therapy

Carboplatin + Paclitaxel + Nivolumab (any histology)138,u,w,kk

Day 1: Cisplatin AUC 5 OR 6 IV

Day 1: Paclitaxel 175mg/m2 or 200mg/m2 IV

Day 1: Nivolumab 360mg IV.

Repeat cycle every 3 weeks for up to 3 cycles.

Cisplatin + Pemetrexed + Nivolumab (nonsquamous)138,u,v,kk

Day 1: Cisplatin 75mg/m2 IV

Day 1: Pemetrexed 500mg/m2 IV

Day 1: Nivolumab 360mg IV.

Repeat cycle every 3 weeks for up to 3 cycles.

Cisplatin + Gemcitabine + Nivolumab (squamous)138,u,dd,kk

Day 1: Cisplatin 75mg/m2 IV

Days 1,8: Gemcitabine 1,000mg/m2 or 1,250mg/m2 IV

Day 1: Nivolumab 360mg IV.

Repeat cycle every 3 weeks for up to 3 cycles.

▶Chemotherapy Regimens Used with Radiation Therapy (RT)

Concurrent Chemoradiation Regimensll

Preferred (Nonsquamous)

Carboplatin + Paclitaxel139,140,w,mm-pp

Premedication is required.

Day 1: Paclitaxel 45-50mg/m2 IV over 60 minutes, followed by:

Day 1: Carboplatin AUC 2 IV over 30 minutes.

Repeat induction therapy weekly for 7 weeks with RT.

OR

Day 1: Paclitaxel 45-50mg/m2 IV over 60 minutes, followed by:

Day 1: Carboplatin AUC 2 IV over 30 minutes.

Repeat induction therapy weekly for 7 weeks with RT, conditionally followed by:

Day 1: Paclitaxel 200mg/m2 IV over 3 hours, followed by:

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat consolidation therapy every 3 weeks for 2 cycles starting 2-4 weeks after completion of concurrent chemoradiation.

Carboplatin + Pemetrexed128,v,mm-oo

Premedication is required.

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes followed by:

Day 1: Carboplatin AUC 5 IV over 30 minutes

Repeat cycle every 3 weeks for 4 cycles with RT.

Cisplatin + Etoposide141,142,dd,mm-oo

Days 1, 8: Cisplatin 50mg/m2 IV over 60 minutes

Days 1-5: Etoposide 50mg/m2 IV over 60 minutes.

Repeat cycle every 4 weeks for 2 cycles with RT.

Cisplatin + Pemetrexed143,144,dd,mm-pp

Premedication is required.

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes

Day 1: Cisplatin 75mg/m2 IV over 60 minutes.

Repeat induction therapy every 3 weeks for 3 cycles with RT.

OR

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes

Day 1: Cisplatin 75mg/m2 IV over 60 minutes.

Repeat induction therapy every 3 weeks for 3 cycles with RT, conditionally followed by:

Day 1: Pemetrexed 500mg/m2 over 10 minutes.

Repeat consolidation therapy every 3 weeks for 4 cycles following concurrent chemotherapy/RT.

Preferred (Squamous)

Carboplatin + Paclitaxel138,139,w,mm-pp

Premedication is required.

Day 1: Paclitaxel 45-50mg/m2 IV over 60 minutes, followed by:

Day 1: Carboplatin AUC 2 IV over 30 minutes.

Repeat induction therapy weekly for 7 weeks with RT.

OR

Day 1: Paclitaxel 45-50mg/m2 IV over 60 minutes, followed by:

Day 1: Carboplatin AUC 2 IV over 30 minutes.

Repeat induction therapy weekly for 7 weeks with RT, conditionally followed by:

Day 1: Paclitaxel 200mg/m2 IV over 3 hours, followed by:

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat consolidation therapy every 3 weeks for 2 cycles starting 2-4 weeks after completion of concurrent chemoradiation.

Cisplatin + Etoposide141,142,dd,mm-oo

Days 1, 8: Cisplatin 50mg/m2 IV over 60 minutes

Days 1-5: Etoposide 50mg/m2 IV over 60 minutes.

Repeat cycle every 4 weeks for 2 cycles with RT.

Consolidation Immunotherapy for Patients with Unresectable Stage II/III NSCLC, PS 0-1, and No Disease Progression After 2 or More Cycles of Definitive Concurrent Chemoradiationpp

Durvalumab

(Category 1 for Stage III; Category 2A for Stage II)145-148,u

Day 1: Durvalumab 10mg/kg IV over 60 minutes.

Repeat cycle every 2 weeks for a maximum of 1 year.

OR

Day 1: Durvalumab 1,500mg over 60 minutes (for patients with body weight ≥30 kg).

Repeat cycle every 4 weeks for a maximum of 1 year.

▶Emerging Biomarkers to Identify Novel Therapies for Patients with Metastatic NSCLC

High-level MET Amplification

Crizotinib48,150,151

Days 1-28: Crizotinib 250mg orally twice daily.

Repeat cycle every 4 weeks.

Capmatinib65,66

Days 1-28: Capmatinib 400mg orally twice daily.

Repeat cycle every 4 weeks.

Tepotinib67,149

Days 1-28: Tepotinib 450mg orally once daily.

Repeat cycle every 4 weeks.

ERBB2 (HER2) Mutations

Ado-trastuzumab emtansine152,153

Day 1: Ado-trastuzumab emtansine 3.6mg/kg IV.

Repeat cycle every 3 weeks.

Fam-trastuzumab deruxtecan-nxki154,155

Day 1: Fam-Trastuzumab deruxtecan-nxki 6.4mg/kg IV.

Repeat cycle every 3 weeks.

a  For performance status (PS) 0-4

b  For EGFR mutation discovered during first-line treatment, complete planned therapy, including maintenance therapy or interrupt, followed by Osimertinib (preferred) or Erlotinib or Afatinib or Dacomitinib, or Erlotinib + Ramucirumab or Erlotinib + Bevacizumab.

c  If systemic therapy regimen contains an immune checkpoint inhibitor, physicians should be aware of the long half-life of such drugs and data reporting adverse events when using osimertinib in combination with or following checkpoint inhibitors. Schoenfeld AJ, et al. Ann Oncol. 2019;30:839-844; Oshima Y, et al. JAMA Oncol. 2018;4:1112-1115. Oxnard GR, et al. Ann Oncol. 2020;31:507-516.

d  This agent may cause severe diarrhea. Evaluate risk of diarrhea prior to initiation of therapy, then monitor for episodes of diarrhea as clinically indicated for potential dose modification or discontinuation. Diarrhea may be treated with antidiarrheals (eg, loperamide). Patients may require IV hydration and electrolyte replacement.

e  This regimen may be associated with mucositis. Evaluate risk of mucositis prior to initiation of therapy, then monitor for episodes of mucositis as clinically indicated for potential dose modification or discontinuation. Patients may also require symptom management including topical mouthwashes, opioids for pain relief, IV hydration, and nutritional support.

f  An FDA-approved biosimilar is an appropriate substitute for Bevacizumab.

g  Criteria for treatment with Bevacizumab: non-squamous NSCLC, and no recent history of hemoptysis.

h  For Ramucirumab: Premedication for infusion reactions is required. The recommended dosing is: Diphenhydramine 12.5-50mg IV or orally 30 minutes pre-Ramucirumab.

I  Afatinib + Cetuximab (Days 1-14: Afatinib 40mg orally daily; Day 1: Cetuximab 500mg/m2 IV. Repeat cycle every 2 weeks.) (Janjigian YY, et al. Cancer Discov. 2014;4(9):1036-1045.)

J  If EGFR mutation discovered during first-line systemic therapy, complete planned systemic therapy, including maintenance therapy, or interrupt, followed by Afatinib (preferred) or Osimertinib (preferred) or Erlotinib or Gefitinib or Dacomitinib.

k  For Amivantamab-vmjw: Premedication for infusion reactions is required. The recommended dosing is:

• For first and second infusion: Methylprednisolone 40mg or dexamethasone 10mg IV 45-60 minutes pre-Amivantamab-vmjw. For subsequent infusions (if first and second tolerated): Methylprednisolone or Dexamethasone may be omitted AND

• Diphenhydramine 25-50mg IV or orally 15-60 minutes pre-Amivantamab-vmjw AND

• Acetaminophen 650-1,000mg IV or orally 15-60 minutes pre-Amivantamab-vmjw

l  This agent may cause severe diarrhea. Evaluate risk of diarrhea prior to initiation of therapy, then monitor for episodes of diarrhea as clinically indicated for potential dose modification or discontinuation. Diarrhea may be treated with antidiarrheals (eg, loperamide). Patients may require IV hydration and electrolyte replacement.

m  If ALK rearrangement discovered during first-line systemic therapy, complete planned systemic therapy, including maintenance therapy, or interrupt, followed by Alectinib (preferred) or Brigatinib (preferred) or Lorlatinib (preferred) or Ceritinib or Crizotinib

n  This agent may cause gastrointestinal toxicities, including both constipation and diarrhea. Evaluate risk prior to initiation of therapy. Patients may require prophylaxis or treatment of symptoms with a bowel regimen, antidiarrheals, intravenous hydration and/or electrolyte replacement. Monitor for symptoms as clinically indicated for potential dose modification or discontinuation.

o  If ROS1 rearrangement discovered during first-line systemic therapy, complete planned systemic therapy, including maintenance therapy, or interrupt, followed by Crizotinib (preferred) or Entrectinib (preferred) or Ceritinib.

p  If BRAF V600E mutation discovered during first-line systemic therapy, complete planned systemic therapy, including maintenance therapy, or interrupt, followed by dabrafenib + trametinib (preferred). Single-agent vemurafenib or dabrafenib are treatment options if the combination of dabrafenib + trametinib is not tolerated.

q  Antipyretic prophylaxis should be considered when clinically warranted. Review drug package insert for specific recommendations.

r  If NTRK1/2/3 gene fusion discovered during first-line systemic therapy, complete planned systemic therapy, including maintenance therapy, or interrupt, followed by Larotrectinib or Entrectinib.

s  If METex14 skipping mutation discovered during first-line systemic therapy, complete planned systemic therapy, including maintenance therapy, or interrupt, followed by Capmatinib (preferred) or Tepotinib (preferred) or Crizotinib.

t  If RET rearrangement discovered during first-line therapy, complete planned systemic therapy, including maintenance therapy, or interrupt, followed by Selpercatinib (preferred), Pralsetinib (preferred), Cabozantinib.

u  Early- and late-onset immune-related adverse events affecting multiple organ systems can occur in patients receiving immune checkpoint inhibitors. Patients with neurologic or life-threatening autoimmune disorders as well as receiving high levels of immunosuppression for their underlying disease should be approached with caution when considering immunotherapy. All patients will require extensive resources including ongoing intensive monitoring and supportive care.

v  For Pemetrexed: premedication and supplemental medications to reduce the incidence and severity of hematologic, gastrointestinal, and cutaneous toxicities are required. The recommended dosing is:

 • Vitamin B12 (cyanocobalamin) 1,000mcg IM during the week preceding the first cycle of Pemetrexed and every 3 cycles thereafter AND

 • Folic acid 400-1000mcg orally daily starting 7 days before ethe first cycle and continuing for 21 days after the last dose of Pemetrexed AND

 • Dexamethasone 4mg orally twice daily for 3 days starting the day prior to Pemetrexed.

w  For Paclitaxel: premedication for hypersensitivity is required:

 • H2 antagonist: Famotidine 20mg IV or orally (or equivalent H2 blocker) 30-60 minutes pre-Paclitaxel AND

 • H1 antagonist: Diphenhydramine 12.5-50mg IV or orally 30-60 minutes pre-Paclitaxel AND

• Dexamethasone 20mg orally approximately 12 and 6 hours pre-Paclitaxel OR Dexamethasone 20 mg IV 30 minutes pre-Paclitaxel

x  If Atezolizumab/Carboplatin/Albumin-bound Paclitaxel or Atezolizumab given (category 1 following Atezolizumab alone).

y  If Atezolizumab/Carboplatin/Paclitaxel/Bevacizumab given.

z  If Pembrolizumab monotherapy given.

aa  If Pembrolizumab/Carboplatin/Pemetrexed or Pembrolizumab/Cisplatin/Pemetrexed given.

bb  If patient has not received platinum-doublet chemotherapy, refer to “systemic therapy”. If patient received platinum chemotherapy and anti-PD-1/PD-L1, refer to “subsequent therapy”.

cc  If Pembrolizumab/Carboplatin/(Paclitaxel or Albumin-bound Paclitaxel) given.

dd  Hydration is required with supplemental electrolytes pre- and post-administration of Cisplatin.

ee  If Nivolumab + Ipilimumab ± chemotherapy given.

ff  If progression on PD-1/PD-L1 inhibitor, using a PD-1/PD-L1 inhibitor is not recommended.

gg  Bevacizumab should be given until progression.

hh For Docetaxel, premedication with Dexamethasone for fluid retention is required. One recommended dosing strategy is:

• Dexamethasone 8 mg orally twice daily for three consecutive days start 1 day prior to Docetaxel administration.

ii  If Bevacizumab was used with a first-line Pemetrexed/platinum chemotherapy regimen.

jj  Osimertinib for patients with completely resected stage IB-IIIA EGFR (exon 19 deletion; L858R) NSCLC who received previous adjuvant chemotherapy or are ineligible to receive platinum-based chemotherapy.

kk  Nivolumab in combination with platinum-based chemotherapy can be used for patients with resectable (tumors ≥4 cm or node positive) NSCLC in the neoadjuvant setting. If an immune checkpoint inhibitor is used in the pre-operative setting, an immune checkpoint inhibitor should not be used in the adjuvant setting.

ll  For patients with superior sulcus tumors, the recommendation is for 2 cycles concurrent with radiation therapy and 2 more after surgery.

mm  Regimens can be used as preoperative/adjuvant chemotherapy/radiotherapy.

nn  Regimens can be used as definitive concurrent chemotherapy/radiotherapy.

oo  For eligible patients, Durvalumab may be used after noted concurrent chemo/radiotherapy regimens.

pp  If using Durvalumab, an additional 2 cycles of chemotherapy is not recommended.

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