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 only provided to supplement the latest treatment strategies.

These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The National Comprehensive Cancer Network 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 NCCN 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.

▶Systemic Therapy for Advanced or Metastatic Cancer1

REGIMEN

DOSING

Sensitizing EGFR Mutation Positive: First-Line

Preferred

Osimertinib (Category 1)2-5,a-c

Osimertinib 80mg orally once daily.

Other Recommended Regimens

Afatinib (Category 1)6-8,a-c

Afatinib 40mg orally once daily.

Dacomitinib (Category 1)9,10,a-c

Dacomitinib 45mg orally once daily.

Erlotinib (Category 1)11-16,a-c

Erlotinb 150mg orally once daily.

Erlotinib + Ramucirumab11,17,18,a-c

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)19-22,a-c

Gefitinib 250mg orally once daily.

Useful in Certain Circumstances

Erlotinib + Bevacizumab (Category 2B)11,23,24,d

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.

Sensitizing EGFR Mutation Positive: Subsequent Therapy

Afatinib (Category 1)6-8,a-c

Afatinib 40mg orally once daily.

Afatinib + Cetuximab6,25,26,a-c

Days 1-14: Afatinib 40mg orally once daily

Day 1: Cetuximab 500mg/m2 IV.

Repeat cycle every 2 weeks.

Dacomitinib (Category 1)9,10,a-c

Dacomitinib 45mg orally once daily.

Erlotinib + Bevacizumab (Category 2B)11,23,24,d

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.

Erlotinib + Ramucirumab11,17,18

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)19-22,a-c

Gefitinib 250mg orally once daily.

Osimertinib2-5,a-c

Osimertinib 80mg orally once daily.

ALK Rearrangement-Positive: First-Line Therapy

Preferred

Alectinib (Category 1)27-30,a,e

Alectinib 600mg orally twice daily.

Other Recommended Regimens

Brigantinb (Category 1)31-33,a,e

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

Days 8-28: Brigatinib 180mg orally once daily

Administer for one 28-day cycle, followed by:

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

Repeat cycle every 4 weeks.

Ceritinib (Category 1)34-38,a,e

Ceritinib 450mg orally once daily.

Useful in Certain Circumstances

Crizotinib (Category 1)30,39-42,a,e

Crizotinib 250mg orally twice daily.

ALK Rearrangement-Positive: Subsequent Therapy

Alectinib27-30,a

Alectinib 600mg orally twice daily.

Brigatinib31-33,a

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

Days 8-28: Brigatinib 180mg orally once daily

Administer for one 28-day cycle, followed by:

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

Repeat cycle every 4 weeks.

Ceritinib34-38,a

Ceritinib 450mg orally once daily.

Crizotinib30,39-42,a

Crizotinib 250mg orally twice daily.

Lorlatinib43-45,a

Lorlatinib 100mg orally once daily.

ROS1 Rearrangement-Positive: First-Line Therapy

Preferred

Crizotinib30.39-42,a,f

Crizotinib 250mg orally twice daily.

Entrectinib46-47,a,f

Entrectinib 600mg orally once daily.

Other Recommended Regimens

Ceritinib34-38,a,f

Ceritinib 450mg orally once daily.

BRAF V600E Mutation Positive: First-Line Therapy

Preferred

Dabrafenib + Trametinib48-51,g,h

Dabrafenib 150mg orally twice daily

Trametinib 2mg orally once daily.

Other Recommended Regimens

Dabrafenib46,52,53,g,h

Dabrafenib 150mg orally twice daily.

Vemurafenib54-56,g,h

Vemurafenib 960mg orally twice daily.

Useful in Certain Circumstances

See Initial systemic therapy options for Adenocarcinoma or Squamous Cell Carcinoma1

NTRK Gene Fusion-Positive: First-Line

Preferred

Entrectinib46-47,i

Entrectinib 600mg orally once daily.

Larotrectinib57-59,i

Larotrectinib 100mg orally twice daily.

Useful in Certain Circumstances

See Initial systemic therapy options for Adenocarcinoma or Squamous Cell Carcinoma1

MET Exon 14 Skipping Mutation: First-Line

Preferred

Capmatinib60-61,j

Capmatinib 400mg orally twice daily.

Useful in Certain Circumstances

Crizotinib30,39-42,j

Crizotinib 250mg orally twice daily.

See Initial systemic therapy options for Adenocarcinoma or Squamous Cell Carcinoma1

RET Rearrangement-Positive: First-Line

Preferred

Pralsetinib62,63,k

Pralsetinib 400mg orally once daily.

Selpercatinib64,65,k

Selpercatinib (less than 50 kg): 120 mg orally twice daily.

Selpercatinib (50 kg or greater): 160 mg orally twice daily.

Useful in Certain Circumstances

Cabozantinib66,67,k

Cabozantinib 60mg orally once daily.

Vandetanib (Category 2B)68,69,k

Vandetanib 300mg orally once daily (starting dose).

Other Recommended Regimens

See Initial systemic therapy options for Adenocarcinoma or Squamous Cell Carcinoma1

PD-L1 Expression-Positive (≥50%) and EGFR, ALK, ROS1, BRAF, MET Exon 14 Skipping Mutation, and RET Negative, and No Contraindications to PD-1 or PD-L1 Inhibitors (PS 0-2): First-Line Therapy

Adenocarcinoma, Large Cell, NSCLC NOSl

Preferred

Atezolizumab70,72,l

Day 1: Atezolizumab 1,200mg IV.

Repeat cycle every 3 weeks.

OR

Day 1: Atezolizumab 840mg IV

Repeat cycle every 2 weeks.

OR

Day 1: Atezolizumab 1,680mg IV

Repeat cycle every 4 weeks.

Carboplatin + Pemetrexed + Pembrolizumab (Category 1)73-75,l

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

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

Day 1: Carboplatin AUC 5 IV over 30 minutes.

Repeat every 3 weeks for 4-6 cycles.e

Cisplatin + Pemetrexed + Pembrolizumab (Category 1)73,75,76,l

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

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

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

Repeat cycle every 3 weeks for 4-6 cycles.e

Pembrolizumab75-79,l

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 42 days for up to 2 years of therapy.

Other Recommended Regimens

Carboplatin + Albumin-Bound Paclitaxel + Atezolizumab70,80,l

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.

Carboplatin + Paclitaxel + Bevacizumab + Atezolizumab (Category 1)23,70,71,d,l

Day 1: Atezolizumab 1,200mg IV

Day 1: Bevacizumab 15mg/kg IV

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.d

OR

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

Day 1: Bevacizumab 15mg/kg IV

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 + Carboplatin81-83

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 42-day cycle, followed by:

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

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

Repeat cycle every 42 days for a maximum of 2 years.

Nivolumab + Ipilimumab + Pemetrexed + Cisplatin81-83

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 42-day cycle, followed by:

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

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

Repeat cycle every 42 days for a maximum of 2 years.

Useful in Certain Circumstances

Nivolumab + Ipilimumab81,82,84

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

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

Repeat cycle every 42 days for a maximum of 2 years.

Squamous Cell Carcinomam

Preferred

Atezolizumab70-72,m

Day 1: Atezolizumab 1,200mg IV.

Repeat cycle every 3 weeks.

OR

Day 1: Atezolizumab 840mg IV.

Repeat cycle every 2 weeks.

OR

Day 1: Atezolizumab 1,680mg IV.

Repeat cycle every 4 weeks.

Carboplatin + Albumin-Bound Paclitaxel + Pembrolizumab (Category 1)75,76,85,m

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.

Carboplatin + Paclitaxel + Pembrolizumab (Category 1)75,76,85,m

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.g

Pembrolizumab (Category 1)75-79,m

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 42 days for up to 2 years of therapy.

Other Recommended Regimens

Nivolumab + Ipilimumab + Paclitaxel + Carboplatin81-83

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 42-day cycle, followed by:

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

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

Repeat cycle every 42 days for a maximum of 2 years.

Useful in Certain Circumstances

Nivolumab + Ipilimumab81,82,84

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

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

Repeat cycle every 42 days for a maximum of 2 years.

PD-L1 Expression-Positive (≥50%) and EGFR, ALK, ROS1, BRAF, MET Exon 14 Skipping Mutation and RET Negative, and No Contraindications to PD-1 or PD-L1 Inhibitors (PS 0-2): Continuation Maintenance Therapy

Adenocarcinoma, Large Cell, NSCLC NOS

Atezolizumab68-70

Day 1: Atezolizumab 1,200mg IV.

Repeat cycle every 3 weeks.

OR

Day 1: Atezolizumab 840mg IV.

Repeat cycle every 2 weeks.

OR

Day 1: Atezolizumab 1,680mg IV.

Repeat cycle every 4 weeks.

Atezolizumab + Bevacizumab (Category 1)23,70,71,d

Day 1: Atezolizumab 1,200mg IV

Day 1: Bevacizumab 15mg/kg IV.

Repeat cycle every 3 weeks.

Pembrolizumab (Category 1)75-79

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 42 days for up to 2 years of therapy.

Pembrolizumab + Pemetrexed (Category 1)73,74,76

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

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

Repeat cycle every 3 weeks for a maximum total of 35 cycles of Pembrolizumab, followed by:

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

Repeat cycle every 3 weeks.l

Squamous Cell Carcinoma

Atezolizumab70-72

Day 1: Atezolizumab 1,200mg IV.

Repeat cycle every 3 weeks.

OR

Day 1: Atezolizumab 840mg IV.

Repeat cycle every 2 weeks.

OR

Day 1: Atezolizumab 1,680mg IV.

Repeat cycle every 4 weeks.

Pembrolizumab (Category 1)75-79

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 42 days for up to 2 years of therapy.

PD-L1 Expression-Positive (1-49%) and EGFR, ALK, ROS1, BRAF, MET Exon 14 Skipping Mutation, and RET Negative, and No Contraindications to PD-1 or PD-L1 Inhibitors (PS 0-2): First-Line Therapy

Adenocarcinoma, Large Cell, NSCLC NOS

Preferred

Carboplatin + Pemetrexed + Pembrolizumab (Category 1)73-77,n

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

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

Day 1: Carboplatin AUC 5 IV over 30 minutes.

Repeat every 3 weeks for 4-6 cycles.e

Cisplatin + Pemetrexed + Pembrolizumab (Category 1)73,75,76,n

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

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

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

Repeat cycle every 3 weeks for 4-6 cycles.e

Other Recommended Regimens

Carboplatin + Albumin-Bound Paclitaxel + Atezolizumab

(Category 1)70.80,n

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.

Carboplatin + Paclitaxel + Bevacizumab + Atezolizumab

(Category 1)23,70,71,n

Day 1: Atezolizumab 1,200mg IV

Day 1: Bevacizumab 15mg/kg IV

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.d

Nivolumab + Ipilimumab + Pemetrexed + Carboplatin81-83

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 42-day cycle, followed by:

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

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

Repeat cycle every 42 days for a maximum of 2 years.

Nivolumab + Ipilimumab + Pemetrexed + Cisplatin81-83

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 42-day cycle, followed by:

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

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

Repeat cycle every 42 days for a maximum of 2 years.

Useful in Certain Circumstances

Nivolumab + Ipilimumab81,82,84

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

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

Repeat cycle every 42 days for a maximum of 2 years.

Pembrolizumab (Category 2B)75-79,o

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 42 days for up to 2 years of therapy.

Squamous Cell Carcinomao

Preferred

Carboplatin + Albumin-Bound Paclitaxel + Pembrolizumab (Category 1)75,76,85,o

Day 1: Pembrolizumab 200mg IVk 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.

Carboplatin + Paclitaxel + Pembrolizumab (Category 1)75,76,85

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.g

Other Recommended Regimens

Nivolumab + Ipilimumab + Paclitaxel + Carboplatin81-83

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 42-day cycle, followed by:

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

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

Repeat cycle every 42 days for a maximum of 2 years.

Useful in Certain Circumstances

Nivolumab + Ipilimumab81,82,84

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

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

Repeat cycle every 42 days for a maximum of 2 years.

Pembrolizumab (Category 2B)75-79,o

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 42 days for up to 2 years of therapy.

PD-L1 Expression-Positive (≥1-49%) and EGFR, ALK, ROS1, BRAF, MET Exon 14 Skipping Mutation and RET Negative, and No Contraindications to PD-1 or PD-L1 Inhibitors: Continuation Maintenance Therapy

Adenocarcinoma, Large Cell, NSCLC NOS

Atezolizumab70-72

Day 1: Atezolizumab 1,200mg IV.

Repeat cycle every 3 weeks.

OR

Day 1: Atezolizumab 840mg IV.

Repeat cycle every 2 weeks.

OR

Day 1: Atezolizumab 1,680mg IV.

Repeat cycle every 4 weeks.

Atezolizumab + Bevacizumab (Category 1)23,70,71,d

Day 1: Atezolizumab 1,200mg IV

Day 1: Bevacizumab 15mg/kg IV.

Repeat cycle every 3 weeks.

Pembrolizumab75-79

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 42 days for up to 2 years of therapy.

Pembrolizumab + Pemetrexed73,74,76

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.

Squamous Cell Carcinoma

Pembrolizumab75-79

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 42 days for up to 2 years of therapy.

Adenocarcinoma, Large Cell, NSCLC NOS (PS 0-1): Initial Systemic Therapyp-s

No Contraindications to PD-1 or PD-L1 Inhibitors

Preferred

Pembrolizumab + Carboplatin + Pemetrexed (Category 1)73-76

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

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

Day 1: Carboplatin AUC 5 IV over 30 minutes.

Repeat every 3 weeks for 4-6 cycles.e

Pembrolizumab + Cisplatin + Pemetrexed (Category 1)73,75,76

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

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

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

Repeat cycle every 3 weeks for 4-6 cycles.

Other Recommended Regimens

Atezolizumab + Carboplatin + Paclitaxel + Bevacizumab

(Category 1)23,70,71,d

Day 1: Atezolizumab 1,200mg IV

Day 1: Bevacizumab 15mg/kg IV

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

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

Atezolizumab + Carboplatin + Albumin-Bound Paclitaxel70,80

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.

Nivolumab + Ipilimumab81,82,84

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

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

Repeat cycle every 42 days for a maximum of 2 years.

Nivolumab + Ipilimumab + Pemetrexed + Carboplatin79-81

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 42-day cycle, followed by:

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

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

Repeat cycle every 42 days for a maximum of 2 years.

Nivolumab + Ipilimumab + Pemetrexed + Cisplatin81-83

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 42-day cycle, followed by:

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

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

Repeat cycle every 42 days for a maximum of 2 years.

Contraindications to PD-1 or PD-L1 Inhibitors

Useful in Certain Circumstances

Bevacizumab + Carboplatin + Paclitaxel (Category 1)23,86,d

Day 1: Bevacizumab 15mg/kg IV

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 6 cycles.

Bevacizumab + Carboplatin + Pemetrexed23,87,d

Day 1: Bevacizumab 15mg/kg IV

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

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Bevacizumab + Cisplatin + Pemetrexed23,88,d

Day 1: Bevacizumab 7.5mg/kg IV

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

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

Repeat cycle every 3 weeks for 4-6 cycles.

Carboplatin + Albumin-Bound Paclitaxel89 (Category 1)

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)90

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)91,92

Days 1-3: Etoposide 100mg/m2 IV over 30 minutes daily

Day 1: Carboplatin AUC 5 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Carboplatin + Gemcitabine (Category 1)91

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)94

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)93

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

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Cisplatin + Docetaxel

(Category 1)90

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

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

Repeat cycle every 3 weeks for 4-6 cycles.

Cisplatin + Etoposide

(Category 1)96

Day 1: Cisplatin 100mg/m2 IV over 60 minutes

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

Repeat cycle every 3 weeks for 4-6 cycles.

Cisplatin + Gemcitabine

(Category 1)95,96

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

Day 1: Cisplatin 75-80mg/m2 IV over 60 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Cisplatin + Paclitaxel

(Category 1)99

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

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

Repeat cycle every 3 weeks for 4-6 cycles.

Cisplatin + Pemetrexed

(Category 1)100

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

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

Repeat cycle every 3 weeks for 4-6 cycles.

Gemcitabine + Docetaxel

(Category 1)101

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)102

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.

Adenocarcinoma, Large Cell, NSCLC NOS (PS 2): Initial Systemic Therapyp-s

Preferred

Carboplatin + Pemetrexed95

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

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Other Recommended Regimens

Carboplatin + Albumin-Bound Paclitaxel89

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 + Docetaxel90

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 + Etoposide91,92

Days 1-3: Etoposide 100mg/m2 IV over 30 minutes daily

Day 1: Carboplatin AUC 5 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Carboplatin + Gemcitabine93

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

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 4 weeks for 4-6 cycles.

Carboplatin + Paclitaxel94

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 Paclitaxel103,104

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.

Docetaxel105,106

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

Repeat cycle every 3 weeks for 4-6 cycles.

Gemcitabine98,107,108

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 + Docetaxel101

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 + Vinorelbine102

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.

Paclitaxel109-111

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.

Pemetrexed112-114

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

Repeat cycle every 3 weeks for 4-6 cycles.

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

Atezolizumab70-72

Day 1: Atezolizumab 1,200mg IV.

Repeat cycle every 3 weeks.

OR

Day 1: Atezolizumab 840mg IV.

Repeat cycle every 2 weeks.

OR

Day 1: Atezolizumab 1,680mg IV.

Repeat cycle every 4 weeks.

Atezolizumab + Bevacizumab (Category 1)23,70,71,d

Day 1: Atezolizumab 1,200mg IV

Day 1: Bevacizumab 15mg/kg IV.

Repeat cycle every 3 weeks.

Bevacizumab (Category 1)23,86,d

Day 1: Bevacizumab 15mg/kg IV.

Repeat cycle every 3 weeks.

Bevacizumab + Pemetrexed

(Category 1)23,87,88,d

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

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

Repeat cycle every 3 weeks.

Gemcitabine (Category 2B)98,107,108

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.

Pemetrexed (Category 1)112-114

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

Repeat every 3 weeks.

Pembrolizumab + Pemetrexed (Category 1)71,72,74

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.

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

Pemetrexed112-114

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

Repeat every 3 weeks.

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

Preferred

Atezolizumab (Category 1)70-72

Day 1: Atezoliziumab 1,200mg IV.

Repeat cycle every 3 weeks.

OR

Day 1: Atezolizumab 840mg IV.

Repeat cycle every 2 weeks.

OR

Day 1: Atezolizumab 1,680mg IV.

Repeat cycle every 4 weeks.

Nivolumab (Category 1)81,115-118

Day 1: Nivolumab 240mg IV over 30 minutes.

Repeat cycle every 2 weeks.

OR

Day 1: Nivolumab 480mg IV over 30 minutes.

Repeat cycle every 4 weeks.

Pembrolizumab (Category 1)75-79

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 42 days for up to 2 years of therapy.

Other Recommended Therapy

Docetaxel105,106

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

Repeat every 3 weeks.

Gemcitabine98,107,108

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.

Pemetrexed112-114

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

Repeat cycle every 3 weeks.

Ramucirumab + Docetaxel17,119

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

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

Repeat cycle every 3 weeks.

Squamous Cell Carcinoma (PS 0-1): Initial Systemic Therapyp-r,t

No Contraindications to PD-1 or PD-L1 Inhibitors

Preferred

Pembrolizumab + Carboplatin + Albumin-Bound Paclitaxel

(Category 1)75,76,85

Day 1: Pembrolizumab 200mg IV over 30 minutes, 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 cycles.

Pembrolizumab + Carboplatin + Paclitaxel (Category 1)75,76,85

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

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

Day 1: Carboplatin AUC 6 over 30 minutes.

Repeat cycle every 3 weeks for 4 cycles.

Other Recommended Regimens

Nivolumab + Ipilimumab81,82,84

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

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

Repeat cycle every 42 days for a maximum of 2 years.

Nivolumab + Ipilimumab + Paclitaxel + Carboplatin79-81

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 42-day cycle, followed by:

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

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

Contraindications to PD-1 or PD-L1 Inhibitors

Useful in Certain Circumstances

Carboplatin + Albumin-Bound Paclitaxel (Category 1)89

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)90

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)93

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

Day 1: Carboplatin AUC 5 IV over 30 minutes.

Repeat cycle ever 4 weeks for 4-6 cycles.

Carboplatin + Paclitaxel

(Category 1)94

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.

Cisplatin + Docetaxel

(Category 1)90

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

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

Repeat cycle every 3 weeks for 4-6 cycles.

Cisplatin + Etoposide

(Category 1)96

Day 1: Cisplatin 100mg/m2 over 60 minutes

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

Repeat cycle every 3 weeks for 4-6 cycles.

Cisplatin + Gemcitabine

(Category 1)97,98

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

Day 1: Cisplatin 75-80mg/m2 IV over 60 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Cisplatin + Paclitaxel

(Category 1)99

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

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

Repeat every 3 weeks for 4-6 cycles.

Gemcitabine + Docetaxel

(Category 1)101

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

Day 8: Docetaxel 85mg/m2 IV over 30 minutes, followed by:

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

Repeat every 3 weeks for 4-6 weeks.

Gemcitabine + Vinorelbine

(Category 1)102

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

Day 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): Initial Systemic Therapyp-r,t

Preferred

Carboplatin + Albumin-Bound Paclitaxel89

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 + Gemcitabine93

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

Day 1: Carboplatin AUC 5 IV over 30 minutes.

Repeat cycle ever 4 weeks for 4-6 cycles.

Carboplatin + Paclitaxel94

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.

Other Recommended Regimens

Carboplatin + Docetaxel90

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 + Etoposide91,92

Days 1-3: Etoposide 100mg/m2 IV over 30 minutes daily

Day 1: Carboplatin AUC 5 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Useful in Certain Circumstances

Albumin-Bound Paclitaxel103,104

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.

Docetaxel105,106

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

Repeat cycle every 3 weeks for 4-6 cycles.

Gemcitabine98,107,108

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 + Docetaxel101

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 cycle every 3 weeks for 4-6 weeks.

Gemcitabine + Vinorelbine101

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 every 3 weeks for 4-6 cycles.

Paclitaxel109-111

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 0-2): Continuation Maintenance

Gemcitabine (Category 2B)98,107,108

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.

Pembrolizumab75-79

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 42 days for up to 2 years of therapy.

Squamous Cell Carcinoma (PS 0-2): Switch Maintenance

Docetaxel (Category 2B)105,106

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

Repeat cycle every 3 weeks.

Squamous Cell Carcinoma (PS 0-2): Subsequent Therapy

Preferred (No Previous Immunotherapy)

Atezolizumab (Category 1)70-72

Day 1: Atezolizumab 1,200mg IV.

Repeat cycle every 3 weeks.

OR

Day 1: Atezolizumab 840mg IV.

Repeat cycle every 2 weeks.

OR

Day 1: Atezolizumab 1,680mg IV.

Repeat cycle every 4 weeks.

Nivolumab (Category 1)81,115-118

Day 1: Nivolumab 240mg IV over 30 minutes.

Repeat cycle every 2 weeks.

OR

Day 1: Nivolumab 480mg IV over 30 minutes.

Repeat cycle every 4 weeks.

Pembrolizumab (Category 1)75-79

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 42 days for up to 2 years of therapy.

Other Recommended Regimens (No Previous or Previous Immunotherapy)

Docetaxel105,106

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

Repeat cycle every 3 weeks.

Gemcitabine98,107,108

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.

Ramucirumab + Docetaxel17,119

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

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

Repeat cycle every 3 weeks.

▶Chemotherapy Regimens for Neoadjuvant and Adjuvant Therapy1,u,v

REGIMEN

DOSING

Preferred (Nonsquamous)

Cisplatin + Pemetrexed97,100

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

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

Repeat cycle every 3 weeks for 4 cycles.

Preferred (Squamous)

Cisplatin + Gemcitabine97,98

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.

Cisplatin + Docetaxel90

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.

Other Recommended Regimens

Cisplatin + Etoposide120

Day 1: Cisplatin 100mg/m2 IV over 60 minutes

Days 1-3: Etoposide 100mg/m2 IV over 2 hours.

Repeat cycle every 4 weeks for 4 cycles.

Cisplatin + Vinorelbine120-122

Day 1: Cisplatin 75-80mg/m2 IV over 60 minutes

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

Repeat cycle every 3 weeks for 4 cycles.

OR

Days 1 and 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 60 minutes

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 + Gemcitabine123

Days 1 and 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 + Paclitaxel94,124

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 + Pemetrexed125 (non-squamous)

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.

▶Chemotherapy Regimens Used With Radiation Therapy (RT)1,w

Concurrent Chemotherapy/RT Regimens

Preferred (Nonsquamous)

Carboplatin + Paclitaxel126,127,x-z

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 radiation.

Carboplatin + Paclitaxel126,127,y,aa

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 radiation, conditionally followed by:

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

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 + Pemetrexed114,x-z

Day 1: Carboplatin AUC 5 IV over 30 minutes

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

Repeat cycle every 3 weeks for 4 cycles with radiation.

Cisplatin + Etoposide128,129,x-z

Days 1 and 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 radiation.

Cisplatin + Pemetrexed129,130, x-z

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

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

Repeat induction therapy every 3 weeks for 3 cycles with radiation,

Cisplatin + Pemetrexed130,131,y,aa

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 radiation, conditionally followed by:

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

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

Preferred (Squamous)

Carboplatin + Paclitaxel126,127,x-z

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 radiation.

Carboplatin + Paclitaxel126,127,y,aa

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 radiation, conditionally followed by:

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

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 + Etoposide128,129,x-z

Days 1 and 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 radiation.

▶Consolidation Therapy for Patients With Unresectable Stage III NSCLC, PS 0-1, and No Disease Progression After 2 or More Cycles of Definitive ChemoRT1

Note: For patients with unresectable stage III NSCLC, PS 0-1, and no disease progression after 2 or more cycles of definitive chemoradiation.

Durvalumab

(Category 1)132-134, z,aa,bb

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

Repeat cycle every 2 weeks for a maximum of 12 months.

a For performance status 0-4.

b 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 combining checkpoint inhibitors with osimertinib. Schoenfeld AJ, Arbour KC, Rizvi H, et al. Severe immune-related adverse events are common with sequential PD(L)-1 blockade and osimertinib. Ann Oncol. 2019;30:839-844; Oshima Y, Tanimoto T, Yuji K, Tojo A. EGFR-TKI-associated interstitial pneumonitis in nivolumab-treated patients with non-small cell lung cancer. JAMA Oncol. 2018;3:1112-1115. Ahn M-J, Yang J, Yu H, et al. Results from TATTON phase 1b trial. J Thorac Oncol. 2016;11:S115 (abstr. 1360).

c If EGFR mutation discovered during first-line systemic therapy, complete planned systemic therapy, including maintenance therapy or interrupt, followed by Osimertinib (preferred) or Erlotinib or Afatinib or Gefitinib or Dacomitanib or Erlotinib + Ramucirumab or Erlotinib + Bevacizumab (Category 2B).

d Criteria for treatment with bevacizumab, non-squamous NSCLC, and no recent history of hemoptysis. Bevacizumab should not be given as a single agent. An FDA-approved biosimilar is an appropriate substitute for bevacizumab.

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

f 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.

g If BRAF V600E mutation discovered during first-line systemic therapy, complete planned systemic therapy, including maintenance therapy, or interrupt, followed by Dabrafenib + Trametinib.

h Single-agent vemurafenib or dabrafenib are treatment options if the combination of Dabrafenib + Trametinib is not tolerated.

i If NTRK gene fusion discovered during first-line systemic therapy, complete planned systemic therapy, including maintenance therapy, or interrupt, followed by Larotrectinib or Entrectinib.

j If MET exon 14 skipping mutation discovered during first-line systemic therapy, complete planned systemic therapy, including maintenance therapy, or interrupt, followed by Capmatinib or Crizotinib.

k If RET rearrangement discovered during first-line systemic therapy, complete planned systemic therapy, including maintenance therapy, or interrupt, followed by Selpercatinib (preferred) or Pralsetinib (preferred) or Cabozantinib or Vandetanib (Category 2B).

l See Atezolizumab, Atezolizumab + Bevacizumab (Category 1), Pembrolizumab (Category 1), or Pembrolizumab + Pemetrexed (Category 1) continuation maintenance if response or stable disease.

m See Pembrolizumab (Category 1) or Atezolizumab continuation maintenance if response or stable disease.

n See Pembrolizumab (Category 1), Pembrolizumab + Pemetrexed (Category 1), Atezolizumab + Bevaciumab (Category 1), or Atezolizumab continuation if response or stable disease.

o See Pembrolizumab continuation maintenance if response or stable disease.

p Albumin-bound paclitaxel may be substituted for either paclitaxel or docetaxel in patients who have experienced hypersensitivity reactions after receiving paclitaxel or docetaxel despite premedication, or for patients where the standard premedications (ie, dexamethasone, H2 blockers, H1 blockers) are contraindicated.

q Carboplatin-based regimens are often used for patients with comorbidities or those who cannot tolerate cisplatin.

r If progression on a PD-1/PD-L1 inhibitor, switching to another PD-1/PD-L1 inhibitor is not routinely recommended.

s See Bevacizumab (Category 1), Pemetrexed (Category 1), Bevacizumab + Pemetrexed, Pembrolizumab + Pemetrexed (Category 1), Atezolizumab + Bevacizumab (Category 1), Atezolizumab, or Gemcitabine (Category 2B) continuation maintenance or Pemetrexed switch maintenance if response or stable disease.

t See Pembrolizumab, Gemcitabine (Category 2B), continuation maintenance or Docetaxel (Category 2B) switch maintenance if response or stable disease.

u After surgical evaluation, patients likely to receive adjuvant chemotherapy may be treated with induction chemotherapy as an alternative.

v All regimens can be used for sequential chemotherapy/RT.

w Concurrent chemotherapy/RT is recommended for patients with inoperable stage II (node-positive) and stage III NSCLC. Sequential chemotherapy/RT or RT alone is appropriate for frail patients unable to tolerate concurrent therapy.

x Regimen can be used as preoperative/adjuvant chemotherapy/RT.

y Regimen can used as definitive concurrent chemotherapy RT.

z For eligible patients, durvalumab may be used after noted concurrent chemo/RT regimens.

aa If using durvalumab, an additional 2 cycles of chemotherapy is not recommended, if patients have not received full-dose chemotherapy concurrent with RT.

bb Durvalumab is not recommended for patients following definitive surgical resection.

References

 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology™, Non-small Cell Lung Cancer. V8.2020. Available at: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed October 5, 2020.

 2. Osimertinib (Tagrisso) [package insert]. Wilmington, DE: AztraZeneca Pharmaceuticals; 2019.

 3. Mok TS, Wu Y-L, Ahn M-J, et al. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017;376:629-640.

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