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. 4. Ramalingam SS, Yang JC, Lee CK, et al. Osimertinib As first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer. J Clin Oncol. 2018;36:841-849. 5. Soria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378:113-125. 5. Afatinib (Gilotrif) [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.: 2019. 7. Sequist LV, Yang JC, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013;31:3327-3334. 8. Yang JC, Wu YL, Schuler M, et al. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015;16:141-151. 9. Dacomitinib (Vizimpro) [package insert]. New York, NY: Pfizer, Inc.; 2018. 10. Wu YL, Cheng Y, Zhou X, et al. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18:1454-1466. 11. Erlotinib (Tarceva) [package insert]. South San Francisco, CA: Genentech Inc. 2016. 12. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005;353:123-132. 13. Cappuzzo F, Ciuleanu T, Stelmakh L, et al. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2010;11:521-529. 14. Pérol M, Chouaid C, Pérol D, et al. Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-small-celeval lung cancer. J Clin Oncol. 2012;30:3516-3524. 15. Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small cell lung cancer (EURTAC): a multicenter, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13:239-246. 16. Paik PK, Varghese AM, Sima CS, et al. Response to erlotinib in patients with EGFR mutant advanced non-small cell lung cancers with a squamous or squamous-like component. Mol Cancer Ther. 2012;11:2535-2540. 17. Ramucirumab (Cyramza) [package insert]. Indianapolis, IN: Eli Lilly and Co.; 2020. 18. Nakagawa K, Garon EB, Seto T, et al. Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20:1655-1669. 19. Gefitinib (Iressa) [package insert]. Wilmington, DE: AztraZeneca Pharmaceuticals; 2019. 20. Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010;362:2380-2388. 21. Doullaird J-Y, Ostoros G, Cobo M, et al. First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study. Br J Cancer. 2014;110:55-62. 22. Mok TS, Wu Y-L, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361:947-957. 23. Bevacizumab (Avastin) [package insert]. South San Francisco, CA: Genentech, Inc.; 2020. 24. Saito H, Fukuhara T, Furuya N, et al. Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): interim analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Oncol. 2019;20:625-635. 25. Cetuximab (Erbitux) [package insert]. Branchburg, NJ; Eli Lilly and Co.; 2015. 25. Janjigian YY, Smit EF, Groen HJ, et al. Dual inhibition of EGFR with afatinib and cetuximab in kinase inhibitor-resistant EGFR-mutant lung cancer with and without T790M mutations. Cancer Discov. 2014;4:1036-1045. 27. Alectinib (Alecensa) [package insert]. South San Francisco, CA: Genentech Inc.; 2018. 28. Ou SH, Ahn JS, De Petris L, et al. Alectinib in crizotinib-refractory ALK-rearranged non-small-cell lung cancer: A phase II global study. J Clin Oncol. 2016;34:661-668. 29. Shaw AT, Gandhi L, Gadgeel S, et al. Alectinib in ALK-positive, crizotinib-resistant, non-small cell lung cancer: a single-group, multicenter, phase 2 trial. Lancet Oncol. 2016;17:234-242. 30. Peters S, Camidge DR, Shaw AT, et al. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med. 2017;377:829-838. 31. Brigatinib (Alunbrig) [package insert]. Cambridge, MA: Takeda Pharmaceutical Co. Ltd: 2020. 32. Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus crizotinib in ALK-positive non-small-cell lung cancer. N Engl J Med. 2018;379:2027-2039. 33. Kim DW, Tiseo M, Ahn MJ, et al. Brigatinib in patients with crizotinib-refractory anaplastic lymphoma kinase-positive non-small-cell lung cancer: A Randomized, multicenter phase II trial. J Clin Oncol. 2017;35:2490-2498. 34. Ceritinib (Zakadia) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp.; 2019. 35. Cho BC, Kim DW, Bearz A, et al. ASCEND-8: A Randomized phase 1 study of ceritinib, 450 mg or 600 mg, taken with a low-fat meal versus 750 mg in fasted state in patients with anaplastic lymphoma kinase (ALK)-rearranged metastatic non-small cell lung cancer (NSCLC). J Thorac Oncol. 2017;12:1357-1367. 35. Shaw AT, Kim DW, Mehra R, et al. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med. 2014;370:1189-1197. 37. Soria JC, Tan DSW, Chiari R, et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet. 2017;389:917-929. 38. Lim SM, Kim HR, Lee JS, et al. Open-label, multicenter, phase II study of ceritinib in patients with non-small-cell lung cancer harboring ROS1 rearrangement. J Clin Oncol. 2017;35:2613-2618. 39. Crizotinib (Xalkori) [package insert]. New York, NY: Pfizer Inc.; 2019. 40. Solomon BJ, Mok T, Kim DW, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014;371:2167-2177. 41. Shaw AT, Ou SH, Bang YJ, et al. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med. 2014;371:1963-1971. 42. Drilon A, Clark JW, Weiss J, et al. Antitumor activity of crizotinib in lung cancers harboring a MET exon 14 alteration. Nat Med. 2020;26:47-51. 43. Lorlatinib (Lorbrena) [package insert]. New York, NY: Pfizer, Inc.; 2020. 44. Solomon BJ, Besse B, Bauer TM, et al. Lorlatinib in patients with ALK-positive non-small-cell lung cancer: results from a global phase 2 study. Lancet Oncol. 2018;19:1654-1667. 45. Solomon B, Shaw A, Ou S, et al. Phase 2 study of lorlatinib in patients with advanced ALK+/ROS1+ non-small-cell lung cancer [abstract]. J Thorac Oncol. 2017;12(suppl_2; abstr OA 05.06). 45. Entrectinib (Rozlytrek) [package insert]. South San Francisco, CA: Genentech, Inc.; 2019. 47. Drilon A, Siena S, Ou SI, et al. Safety and antitumor activity of the multitargeted pan-TRK, ROS1, and ALK inhibitor entrectinib: Combined results from two phase I trials (ALKA-372-001 and STARTRK-1). Cancer Discov. 2017;7:400-409. 48. Dabrafenib (Dafinlar) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp.; 2019. 49. Trametinib (Mekinist) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp.; 2020. 50. Planchard D, Smit EF, Groen HJM, et al. Dabrafenib plus trametinib in patients with previously untreated BRAFV600E-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial. Lancet Oncol. 2017;18:1307-1316. 51. Planchard D, Besse B, Groen HJM, et al. Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. Lancet Oncol. 2016;17:984-993. 52. Gautschi O, Milia J, Cabarrou B, et al. Targeted therapy for patients with BRAF-mutant lung cancer: Results from the European EURAF cohort. J Thorac Oncol. 2015;10:1451-1457. 53. Planchard D, Kim TM, Mazieres J, et al. Dabrafenib in patients with BRAF(V600E)-positive advanced non-small-cell lung cancer: a single-arm, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016;17:642-650. 54. Vemurafenib (Zelboraf) [package insert]. South San Francisco, CA: Genentech, Inc.; 2017. 55. Peters S, Michielin O, Zimmermann S. Dramatic response induced by vemurafenib in a BRAF V600E-mutated lung adenocarcinoma. Clin Oncol. 2013;31:e341-e344. 55. Gautschi O, Milia J, Cabarrou B, et al. Targeted therapy for patients with BRAF-mutant lung cancer: Results from the European EURAF cohort. J Thorac Oncol. 2015;10:1451-1457. 57. Larotrectinib (Vitrakvi) [package insert]. Stamford, CT: Loxo Oncology, Inc.; 2018. 58. Drilon A, Laetsch TW, Kummar S, et al. Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. N Engl J Med. 2018;378:731-739. 59. Lassen UN, Albert CM, Kummar S, et al. Larotrectinib efficacy and safety in TRK fusion cancer: An expanded clinical dataset showing consistency in an age and tumor agnostic approach [abstract]. Ann Oncol. 2018;29 (suppl_8; abstr 409O). 60. Capmatinib (Tabrecta) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp.; 2020. 61. Wolf J, Seto T, Han J-Y, et al. Capmatinib (INC280) in METΔex14-mutated advanced non-small cell lung cancer (NSCLC): Efficacy data from the phase II GEOMETRY mono-1 study [abstract]. J Clin Oncol. 2019;37(15-suppl):abstr 9004. 62. Pralsetinib (Gavreto) [package insert]. Cambridge, MA: Blueprint Medicines Corp.; 2020. 63. Gainor JF, Curigliano G, Kim D-W, et al. Registrational dataset from the phase I/II ARROW trial of Pralsetinib (BLU-667) in patients (pts0 with advanced RET fusions non-small cell lung cancer (NSCLC. [abstract]. J Clin Oncol. 2020:38(suppl; abstr 9515). 64. Selpercatinib (Retevmo) [package insert]. Indianapolis, IN: Eli Lilly and Co.; 2020. 65. Drilon A, Oxnard G, Wirth L, et al. PL02.08 Registrational results of LIBRETTO-001: a Phase 1/2 trial of LOXO-292 in patients with RET fusion-positive lung cancers [abstract]. J Thorac Oncol. 2019:14:S6-S7. 66. Cabozantinib (Cabometyx) [package insert]. Alameda, CA: Exelixis, Inc.; 2020. 67. Drilon A, Rekhtman N, Arcila M, et al. Cabozantinib in patients with advanced RET-rearranged non-small-cell lung cancer: an open-label, single-centre, phase 2, single-arm trial. Lancet Oncol. 2016;17:1653-1660. 68. Vandetinib (Caprelsa) [package insert]. Cambridge, MA: Genzyme Corp.; 2020. 69. Lee S-H, Lee J-K, Ahn M-J, et al. Vandetanib in pretreated patients with advanced non-small cell lung cancer-harboring RET rearrangement: a phase II clinical trial. Ann Oncol. 2017;28:292-297. 70. Atezolizumab (Tecentriq) [package insert]. South San Francisco, CA: Genentech, Inc: 2020. 71. Socinski MA, Jotte RM, Cappuzzo F, et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med. 2018;378:2288-2301. 72. Spigel D, de Marinis F, Giaccone G, et al. Impower110: Interim overall survival (OS) analysis of a phase III study of atezolizumab (atezo) vs platinum-based chemotherapy (chemo) as first-line (1L) treatment (tx) in PD-L1–selected NSCLC. Ann Oncol. 2019:30:v871-v934. 73. Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018;378:2078-2092. 74. Langer CJ, Gadgeel SM, Borghaei H, et al. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol. 2016;17:1497-1508. 75. Lala M, Li TR, de Alwis DP, et al. A six-weekly dosing schedule for pembrolizumab in patients with cancer based on evaluation using modelling and simulation. Eur J Cancer. 2020;131:68-75 76. Pembrolizumab (Keytruda) [package insert]. Whitehouse Station, NJ: Merck & Co, Inc.; 2020. 77. Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372:2018-2028. 78. Reck M, Rodríguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375:1823-1833. 79. Mok TSK, Wu YL, Kudaba I, et al. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019;393:1819-1830. 80. West H, McCleod M, Hussein M, et al Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20:924-937. 81. Nivolumab (Opdivo) [package insert]. Princeton, NJ: Bristol-Myers Squibb, Inc; 2020. 82. Ipilimumab (Yervoy) [package insert]. Princeton, NJ: Bristol-Myers Squibb Co.; 2020. 83. Reck M, Ciuleanu T-E, Dols MC, et al. Nivolumab (NIVO) + ipilimumab (IPI) + 2 cycles of platinum-doublet chemotherapy (chemo) vs 4 cycles chemo as first-line (1L) treatment (tx) for stage IV/recurrent non-small cell lung cancer (NSCLC): CheckMate 9LA. Presented at: ASCO20 Virtual Scientific Program [abstract]. J Clin Oncol. 2020;38(suppl):abstr 9501. 84. Hellmann MD, Paz-Ares L, Bernabe Caro R, et al. Nivolumab plus ipilimumab in advanced non-small-cell lung cancer. N Engl J Med. 2019;381:2020-2031. 85. Paz-Ares L, Luft A, Vicente D, et al. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med. 2018;379:2040-2051. 86. Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006;355:2542-2550. 87. Patel JD, Socinski MA, Garon EB, et al. PointBreak: a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer. J Clin Oncol. 2013;31:4349-4357. 88. Barlesi F, Scherpereel A, Rittmeyer A, et al. Randomized phase III trial of maintenance bevacizumab with or without pemetrexed after first-line induction with bevacizumab, cisplatin, and pemetrexed in advanced nonsquamous non-small-cell lung cancer: AVAPERL (MO22089). J Clin Oncol. 2013;31:3004-3011. 89. Socinski MA, Bondarenko I, Karaseva NA, et al. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol. 2012;30:2055-2062. 90. Fossella F, Pereira JR, von Pawel J, et al. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol. 2003;21:3016-3024. 91. Klastersky J, Sculier JP, Lacroix H, et al. A randomized study comparing cisplatin or carboplatin with etoposide in patients with advanced non-small-cell lung cancer: European Organization for Research and Treatment of Cancer Protocol 07861. J Clin Oncol. 1990;8:1556-1562. 92. Frasci G, Comella P, Panza N, et al. Carboplatin-oral etoposide personalized dosing in elderly non-small cell lung cancer patients. Gruppo Oncologico Cooperativo Sud-Italia. Eur J Cancer. 1998;34:1710-1714. 93. Danson S, Middleton MR, O’Byrne KJ, et al. Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma. Cancer. 2003;98:542-553. 94. Ohe Y, Ohashi Y, Kubota K, et al. Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: Four-Arm Cooperative Study in Japan. Ann Oncol. 2007;18:317-323. 95. Scagliotti GV, Kortsik C, Dark GG, et al. Pemetrexed combined with oxaliplatin or carboplatin as first-line treatment in advanced non-small cell lung cancer: a multicenter, randomized, phase II trial. Clin Cancer Res. 2005;11:690-696. 96. Cardenal F, López-Cabrerizo MP, Antón A, et al. Randomized phase III study of gemcitabine-cisplatin versus etoposide-cisplatin in the treatment of locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 1999;17:12-18. 97. Scagliotti GV, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008;26:3543-3551. 98. Perol M, Chouaid C, Perot D, et al. Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemicitabine induction chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2012;30:3516-3524. 99. Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002;346;92-98. 100. Kreuter M, Vansteenkiste J, Fischer JR, et al. Randomized phase 2 trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine: the TREAT study. Ann Oncol. 2013;24:986-992. 101. Pujol JL, Breton JL, Gervais R, et al. Gemcitabine-docetaxel versus cisplatin-vinorelbine in advanced or metastatic non-small-cell lung cancer: a phase III study addressing the case for cisplatin. Ann Oncol. 2005;16:602-610. 102. Tan EH, Szczesna A, Krzakowski M, et al. Randomized study of vinorelbine–gemcitabine versus vinorelbine–carboplatin in patients with advanced non-small cell lung cancer. Lung Cancer. 2005;49:233-240. 103. Green MR, Manikhas GM, Orlov S, et al. Abraxane, a novel Cremophor-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. Ann Oncol. 2006;17:1263-1268. 104. Rizvi NA, Riely GJ, Azzoli CG, et al. Phase I/II trial of weekly intravenous 130-nm albumin-bound paclitaxel as initial chemotherapy in patients with stage IV non-small-cell lung cancer. J Clin Oncol. 2008;26:639-643. 105. Fossella FV, DeVore R, Kerr RN, et al. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group. J Clin Oncol. 2000;18:2354-2362. 106. Fidias PM, Dakhil SR, Lyss AP, et al. Phase III study of immediate compared with delayed docetaxel after front-line therapy with gemcitabine plus carboplatin in advanced non-small-cell lung cancer. J Clin Oncol. 2009;27:591-598. 107. Zatloukal P, Kanitz E, Magyar P, et al. Gemcitabine in locally advanced and metastatic non-small cell lung cancer: the Central European phase II study. Lung Cancer. 1998;22:243-250. 108. Sederholm C, Hillerdal G, Lamberg K, et al. Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: the Swedish Lung Cancer Study Group. J Clin Oncol. 2005;23:8380-8388. 109. Lilenbaum RC, Herndon JE 2nd, List MA, et al. Single-agent versus combination chemotherapy in advanced non-small-cell lung cancer: the cancer and leukemia group B (study 9730). J Clin Oncol. 2005;23:190-196. 110. Ceresoli GL, Gregorc V, Cordio S, et al. Phase II study of weekly paclitaxel as second-line therapy in patients with advanced non-small cell lung cancer. Lung Cancer. 2004;44:231-239. 111. Yasuda K, Igishi T, Kawasaki Y, et al. Phase II study of weekly paclitaxel in patients with non-small cell lung cancer who have failed previous treatments. Oncology. 2004;66:347-352. 112. Hanna N, Shepherd FA, Fossella FV, et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004;22:1589-1597. 113. Ciuleanu T, Brodowicz T, Zielinski C, et al. Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study. Lancet. 2009;374:1432-1440. 114. Govindan R, Bogart J, Stinchcombe T, et al. Randomized phase II study of pemetrexed, carboplatin, and thoracic radiation with or without cetuximab in patients with locally advanced unresectable non-small-cell lung cancer: Cancer and Leukemia Group B trial 30407. J Clin Oncol. 2011;29:3120-3125. 115. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373:123-135. 116. Long GV, Tykodi SS, Schneider JG, et al. Assessment of nivolumab exposure and clinical safety of 480 mg every 4 weeks flat-dosing schedule in patients with cancer. Ann Oncol. 2018;29:2208-2213. 117. Horn L, Spigel DR, Vokes EE, et al. Nivolumab versus docetaxel in previously treated patients with advanced non-small-cell lung cancer: Two-year outcomes from two randomized, open-label, phase III trials (CheckMate 017 and CheckMate 057). J Clin Oncol. 2017;35:3924-3933. 118. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373:1627-1639. 119. Garon EB, Ciuleanu TE, Arrieta O, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double- blind, randomised phase 3 trial. Lancet. 2014;384:665-673. 120. Arriagada R, Bergman B, Dunant A, et al. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004;350:351-360. 121. Douillard JY, Rosell R, De Lena M, et al. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol. 2006;7:719-727. 122. Winton T, Livingston R, Johnson D, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med. 2005;352:2589-2597. 123. Usami N, Yokoi K, Hasegawa Y, et al. Phase II study of carboplatin and gemcitabine as adjuvant chemotherapy in patients with completely resected non-small cell lung cancer: a report from the Central Japan Lung Study Group, CJLSG 0503 trial. Int J Clin Oncol. 2010;15:583-587. 124. Strauss GM, Herndon JE 2nd, Maddaus MA, et al. Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups. J Clin Oncol. 2008;26:5043-5051. 125. Zhang L, Ou W, Liu Q, et al. Pemetrexed plus carboplatin as adjuvant chemotherapy in patients with curative resected non-squamous non-small cell lung cancer. Thorac Cancer. 2014;5:50-56. 126. Belani CP, Choy H, Bonomi P, et al. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol. 2005;23:5883-5891. 127. Bradley JD, Paulus R, Romaki R, et al. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol. 2015;15:187-199. 128. Albain KS, Crowley JJ, Turrisi AT 3rd, et al. Concurrent cisplatin, etoposide, and chest radiotherapy in pathologic stage IIIB non-small-cell lung cancer: a Southwest Oncology Group phase II study, SWOG 9019. J Clin Oncol. 2002;20:3454-3460. 129. Liang J, Bi N, Wu S, et al. Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial. Ann Oncol. 2017;28:777-783. 130. Senan S, Brade A, Wang L-H, et al. PROCLAIM: Randomized phase III trial of pemetrexed-cisplatin or etoposide-cisplatin plus thoracic radiation therapy followed by consolidation chemotherapy of locally advanced nonsquamous non-small-cell lung cancer. J Clin Oncol. 2016;34:953-062. 131. Choy H, Gerber DE, Bradley JD, et al. Concurrent pemetrexed and radiation therapy in the treatment of patients with inoperable stage III non-small cell lung cancer: a systematic review of completed and ongoing studies. Lung Cancer. 2015;87:232-240. 132. Durvalumab (Imfinzi) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals, LP: 2020. 133. Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med. 2017;377:1919-1929. 134. Antonia SJ, Villegas A, Daniel D, et al. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med. 2018;379:2342-2350.
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