Non-Small Cell Lung Cancer Treatment Regimens

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NON-SMALL CELL LUNG CANCER TREATMENT REGIMENS

10/2017

© 2017 Haymarket Media, Inc.

Clinical Trials: The National Comprehensive Cancer Network 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 health care team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are provided only to supplement the latest treatment strategies.

These Guidelines are a work in progress that may be refined as often as new significant data become available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient's care or treatment. The 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.

Chemotherapy Regimens for Neoadjuvant and Adjuvant Therapy1

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

REGIMEN

DOSING

Cisplatin + vinorelbine2–4

Days 1 and 8: Cisplatin 50mg/m2 IV

Days 1, 8, 15 and 22: Vinorelbine 25mg/m2 IV.

Repeat cycle every 4 weeks for 4 cycles.

OR

Day 1: Cisplatin 100mg/m2 IV

Days 1, 8, 15 and 22: Vinorelbine 30mg/m2 IV.

Repeat cycle every 4 weeks for 4 cycles.

OR

Day 1: Cisplatin 75–80mg/m2

Days 1 and 8: Vinorelbine 25–30mg/m2.

Repeat every 3 weeks for 4 cycles.

Cisplatin + etoposide3

Day 1: Cisplatin 100mg/m2 IV

Days 1–3: Etoposide 100mg/m2 IV.

Repeat cycle every 4 weeks for 4 cycles.

Cisplatin + gemcitabine5

Day 1: Cisplatin 75mg/m2 IV

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

Repeat cycle every 3 weeks.

Cisplatin + docetaxel6

Day 1: Docetaxel 75mg/m2 IV + cisplatin 75mg/m2 IV.

Repeat every 3 weeks for 4 cycles.

Cisplatin + pemetrexed7

Day 1: Cisplatin 75mg/m2 IV + pemetrexed 500mg/m2 IV.*

Repeat every 3 weeks for 4 cycles.

For patients with comorbidities or patients not able to tolerate cisplatin1

Paclitaxel + carboplatin8

Day 1: Paclitaxel 200mg/m2 IV + carboplatin AUC 6mg min/mL IV.

Repeat cycle every 3 weeks for 4 cycles.

Chemotherapy Regimens Used With Radiation Therapy (RT)1

Concurrent Chemotherapy/RT1

Cisplatin + etoposide9,10,a,b

Days 1, 8, 29 and 36: Cisplatin 50mg/m2 IV

Days 1–5 and 29–33: Etoposide 50mg/m2 IV

Concurrent thoracic radiotherapy 1.8Gy/day for 5 days/week (total dose, 61Gy).

Cisplatin + vinblastine10,a,b

Days 1 and 29: Cisplatin 100mg/m2 IV

Days 1, 8, 15, 22 and 29: Vinblastine 5mg/m2 IV with concurrent thoracic radiotherapy (total dose, 60Gy).

Carboplatin + pemetrexed (nonsquamous)11,a,b

Day 1: Carboplatin AUC 5mg min/mL IV

Day 1: Pemetrexed 500 mg/m2 IV with concurrent thoracic radiotherapy.

Repeat every 3 weeks for 4 cycles.

Cisplatin + pemetrexed (nonsquamous)12,13

Day 1: Cisplatin 75 mg/m2 IV.

Day 1: Pemetrexed 500 mg/m2 IV with concurrent thoracic radiotherapy.a,b

Repeat every 3 weeks for 3 cycles ± additional 4 cycles of pemetrexed 500mg/m2.b

Paclitaxel + carboplatin14

Paclitaxel 45-50mg/m2 IV + carboplatin AUC 2mg min/mL IV weekly with concurrent thoracic radiotherapy (total dose, 60Gy)a,b given 5 days per weeks in 2Gy fractionsa,b ± additional 2 cycles of paclitaxel 200mg/m2 and carboplatin AUC 6mg min/mL IV.b

Sequential Chemotherapy/RT (Adjuvant)1

Cisplatin + vinblastine10

Days 1 and 29: Cisplatin 100mg/m2 IV.

Days 1, 8, 15, 22 and 29: Vinblastine 5mg/m2 IV; followed by thoracic radiotherapy with 60Gy in 30 fractions beginning on Day 50.

Paclitaxel + carboplatin15

Day 1: Paclitaxel 200mg/m2 IV over 3 hours + carboplatin AUC 6mg min/mL IV over 1 hour.

Repeat every 3 weeks for 2 cycles; followed by thoracic radiotherapy 63Gy beginning on Day 42.

Consolidation Therapy1

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

Durvalumab16

Day 1: Durvalumab 10mg/kg

Repeat every 2 weeks for up to 12 months.

Systemic Therapy for Advanced & Metastatic Disease1

Principles of Therapy1

The drug regimen with the highest likelihood of benefit, with toxicity deemed acceptable to both the physician and the patient, should be given as initial therapy for advanced lung cancer.

Stage, weight loss, performance status (PS), and gender predict survival.

Platinum-based chemotherapy prolongs survival, improves symptom control, and yields superior quality of life compared to best supportive care.

Histology of NSCLC is important in the selection of systemic therapy.

New agent/platinum combinations have generated a plateau in overall response rate (25%–35%), time to progression (4–6 months), median survival (8–10 months), 1-year survival rate (30%–40%), and 2-year survival rate (10%–15%) in fit patients.

Unfit patients of any age (PS 3–4) do not benefit from cytotoxic treatment, except erlotinib for those who are epidermal growth factor receptor (EGFR) mutation-positive.

First-line Systemic Therapy Options1

Principles of Therapy1

There is superior efficacy and reduced toxicity for cisplatin/pemetrexed in patients with nonsquamous histology compared with cisplatin/gemcitabine.

There is superior efficacy for cisplatin/gemcitabine in patients with squamous histology, in comparison to cisplatin/pemetrexed.

Two drug regimens are preferred; a third cytotoxic drug increases response rate but not survival.

Single-agent therapy may be appropriate in select patients.

Response assessment after 2 cycles, then every 2–4 cycles with CT of known sites of disease with or without contrast or when clinically indicated.

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

Bevacizumab + carboplatin + paclitaxel (Category 1)17,c,d

Day 1: Paclitaxel 200mg/m2 IV + carboplatin AUC 6mg min/mL IV.

Repeat cycle every 3 weeks for 6 cycles.

Day 1: Bevacizumab 15mg/kg IV every 3 weeks until disease progression.

Bevacizumab + carboplatin + pemetrexed18,d

Day 1: Pemetrexed 500mg/m2 IV + carboplatin AUC 6mg min/mL IV + bevacizumab 15mg/kg IV.

Repeat cycle every 3 weeks for up to 4 cycles, followed by:

Day 1: Pemetrexed 500mg/m2 IV + bevacizumab 15mg/kg IV.

Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Bevacizumab + cisplatin + pemetrexed19,d

Day 1: Bevacizumab 7.5mg/kg IV + cisplatin 75mg/m2 IV + pemetrexed 500mg/m2 IV.

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

Day 1: Bevacizumab 7.5mg/kg IV + pemetrexed 500mg/m2 IV.

Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + albumin-bound paclitaxel (Category 1)20

Day 1: Carboplatin AUC 6mg min/mL IV

Days 1, 8, and 15: Nab-paclitaxel 100mg/m2 IV.

Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + docetaxel (Category 1)21,c

Day 1: Docetaxel 75mg/m2 IV + carboplatin AUC 6mg min/mL IV.

Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + etoposide (Category 1)22,23

Day 1: Carboplatin 325mg/m2 IV

Days 1, 2, and 3: Etoposide 100mg/m2 IV.

Repeat cycle every 3 to 4 weeks until disease progression or unacceptable toxicity.

OR

First Course

Day 1: Carboplatin AUC 4mg min/mL IV

Days 1–14: Etoposide 50mg orally twice daily

Second Course

Day 1: Carboplatin AUC 5mg min/mLIV

Days 1–14: Etoposide 50mg orally twice daily

Third Course

Day 1: Carboplatin AUC 5mg min/mLIV

Days 1–21: Etoposide 50mg orally twice daily.

Patients achieving a complete or partial response should receive an additional 3 courses at the same doses given in the third course.

Carboplatin + gemcitabine (Category 1)24

Day 1: Carboplatin AUC 5mg min/mL IV

Days 1, 8, and 15: Gemcitabine 1,000mg/m2 IV

Repeat cycle every 4 weeks for 4 cycles.

Carboplatin + paclitaxel (Category 1)25,c

Day 1: Paclitaxel 200mg/m2 IV + carboplatin AUC 6mg min/mL IV.

Repeat every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + pemetrexed (Category 1)26

Day 1: Pemetrexed 500mg/m2 IV + carboplatin AUC 6mg min/mL IV.

Repeat cycle every 3 weeks for up to 6 cycles.

Cisplatin + docetaxel (Category 1)21,c

Day 1: Cisplatin 75mg/m2 IV + docetaxel 75mg/m2 IV.

Repeat cycle every 3 weeks.

Cisplatin + etoposide (Category 1)27

Day 1: Cisplatin 100mg/m2 IV

Days 1–3: Etoposide 100mg/m2 IV.

Repeat cycle every 3 weeks for up to 6 cycles.

Cisplatin + gemcitabine (Category 1)25,28

Day 1: Cisplatin 80mg/m2 IV

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

Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

OR

Day 1: Cisplatin 75mg/m2 IV

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

Repeat cycle every 3 weeks for up to 6 cycles.

Cisplatin + paclitaxel (Category 1)29,c

Day 1: Paclitaxel 135mg/m2 IV over 24 hours

Day 2: Cisplatin 75mg/m2 IV.

Repeat cycle every 3 weeks.

Cisplatin + pemetrexed (Category 1)28

Day 1: Pemetrexed 500mg/m2 IV + cisplatin 75mg/m2 IV.

Repeat cycle every 3 weeks.

Gemcitabine + docetaxel (Category 1)30,c

Days 1 and 8: Gemcitabine 1,000mg/m2 IV

Day 8: Docetaxel 85mg/m2 IV.

Repeat cycle every 3 weeks for 8 cycles.

Gemcitabine + vinorelbine (Category 1)31

Days 1 and 8: Vinorelbine 25mg/m2 IV + gemcitabine 1,000mg/m2 IV.

Repeat cycle every 3 weeks.

Pembrolizumab + carboplatin + pemetrexed32, f

Days 1: Pembrolizumab 200mg IV + pemetrexed 500mg/m2 IV + carboplatin AUC 5mg • min/mL IV.

Repeat cycle every 3 weeks for up to 4 cycles; followed by:

Days 1: Pembrolizumab 200mg IV every 3 weeks for 24 months

Days 1: Pemetrexed 500mg/m2 IV every 3 weeks (optional, indefinite)

Adenocarcinoma, Large Cell, NSCLC NOS (PS 2)1

Albumin-bound paclitaxel33,c

Day 1: Albumin-bound paclitaxel 260mg/m2 IV.

Repeat cycle every 3 weeks.

Carboplatin + albumin-bound paclitaxel34,35

Day 1: Carboplatin AUC 6mg min/mL IV

Days 1, 8, and 15: Albumin-bound paclitaxel 100mg/m2 IV.

Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + docetaxel21,c

Day 1: Docetaxel 75mg/m2 IV + carboplatin AUC 6mg min/mL IV.

Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + etoposide22,23

Day 1: Carboplatin 325mg/m2 IV

Days 1, 2, and 3: Etoposide 100mg/m2 IV.

Repeat cycle every 3 to 4 weeks until disease progression or unacceptable toxicity.

OR

First Course

Day 1: Carboplatin AUC 4mg min/mL IV

Days 1–14: Etoposide 50mg orally twice daily

Second Course

Day 1: Carboplatin AUC 5mg min/mL IV

Days 1–14: Etoposide 50mg orally twice daily

Third Course

Day 1: Carboplatin AUC 5mg min/mL IV

Days 1–21: Etoposide 50mg orally twice daily.

Patients achieving a complete or partial response should receive an additional 3 courses at the same doses given in the third course.

Carboplatin + gemcitabine24

Day 1: Carboplatin AUC 5mg min/mL IV

Days 1, 8, and 15: Gemcitabine 1,000mg/m2 IV

Repeat cycle every 4 weeks for 4 cycles.

Carboplatin + paclitaxel25,c

Day 1: Paclitaxel 200mg/m2 IV + carboplatin AUC 6mg min/mL IV.

Repeat every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + pemetrexed26

Day 1: Pemetrexed 500mg/m2 IV + carboplatin AUC 6mg min/mL IV.

Repeat cycle every 3 weeks for up to 6 cycles.

Docetaxel36,37,c

Day 1: Docetaxel 75mg/m2 IV over 1 hour.

Repeat cycle every 3 weeks.

Gemcitabine38-40

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

Repeat cycle every 3 weeks.

Gemcitabine + docetaxel30,c

Days 1 and 8: Gemcitabine 1,000mg/m2 IV

Day 8: Docetaxel 85mg/m2 IV.

Repeat cycle every 3 weeks for 8 cycles.

Gemcitabine + vinorelbine31

Days 1 and 8: Vinorelbine 25mg/m2 IV + gemcitabine 1,000mg/m2 IV.

Repeat cycle every 3 weeks.

Paclitaxel41-43, c

Days 1, 8, and 15: Paclitaxel 80mg/m2 IV.

Repeat cycle every 4 weeks for up to 4 cycles.

Pemetrexed44

Day 1: Pemetrexed 500mg/m2 IV.

Repeat cycle every 3 weeks.

Squamous Cell Carcinoma (PS 0-1)1

Carboplatin + albumin-bound paclitaxel (Category 1)20,c

Day 1: Carboplatin AUC 6mg min/mL IV

Days 1, 8, and 15: Albumin-bound paclitaxel 100mg/m2 IV.

Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + docetaxel (Category 1)21,c

Day 1: Docetaxel 75mg/m2 IV + carboplatin AUC 6mg min/mL IV.

Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + gemcitabine (Category 1)22

Day 1: Carboplatin AUC 5mg min/mL IV

Days 1, 8, and 15: Gemcitabine 1,000mg/m2 IV

Repeat cycle every 4 weeks for 4 cycles.

Carboplatin + paclitaxel (Category 1)23,c

Day 1: Paclitaxel 200mg/m2 IV + carboplatin AUC 6mg min/mL IV.

Repeat every 3 weeks until disease progression or unacceptable toxicity.

Cisplatin + docetaxel (Category 1)21,c

Day 1: Cisplatin 75mg/m2 IV + docetaxel 75mg/m2 IV.

Repeat cycle every 3 weeks.

Cisplatin + etoposide (Category 1)27

Day 1: Cisplatin 100mg/m2 IV

Days 1–3: Etoposide 100mg/m2 IV.

Repeat cycle every 3 weeks for up to 6 cycles.

Cisplatin + gemcitabine (Category 1)25,28

Day 1: Cisplatin 80mg/m2 IV

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

Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

OR

Day 1: Cisplatin 75mg/m2 IV

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

Repeat cycle every 3 weeks for up to 6 cycles.

Cisplatin + paclitaxel (Category 1)29,c

Day 1: Paclitaxel 135mg/m2 IV over 24 hours

Day 2: Cisplatin 75mg/m2 IV.

Repeat cycle every 3 weeks.

Gemcitabine + docetaxel (Category 1)30,c

Days 1 and 8: Gemcitabine 1,000mg/m2 IV

Day 8: Docetaxel 85mg/m2 IV.

Repeat cycle every 3 weeks for 8 cycles.

Gemcitabine + vinorelbine (Category 1)31

Days 1 and 8: Vinorelbine 25mg/m2 IV + gemcitabine 1,000mg/m2 IV.

Repeat cycle every 3 weeks.

Squamous Cell Carcinoma (PS 2)1

Albumin-bound paclitaxel33

Day 1: Albumin-bound paclitaxel 260mg/m2 IV.

Repeat cycle every 3 weeks.

Carboplatin + albumin-bound paclitaxel34,35

Day 1: Carboplatin AUC 6mg min/mL IV

Days 1, 8, and 15: Albumin-bound paclitaxel 100mg/m2 IV.

Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + docetaxel21,c

Day 1: Docetaxel 75mg/m2 IV + carboplatin AUC 6mg min/mL IV.

Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + etoposide22,23

Day 1: Carboplatin 325mg/m2 IV

Days 1, 2, and 3: Etoposide 100mg/m2 IV.

Repeat cycle every 3 to 4 weeks until disease progression or unacceptable toxicity.

OR

First Course

Day 1: Carboplatin AUC 4mg min/mL IV

Days 1–14: Etoposide 50mg orally twice daily

Second Course

Day 1: Carboplatin AUC 5mg min/mL IV

Days 1–14: Etoposide 50mg orally twice daily

Third Course

Day 1: Carboplatin AUC 5mg min/mL IV

Days 1–21: Etoposide 50mg orally twice daily.

Patients achieving a complete or partial response should receive an additional 3 courses at the same doses given in the third course.

Carboplatin + gemcitabine24

Day 1: Carboplatin AUC 5mg min/mL IV

Days 1, 8, and 15: Gemcitabine 1,000mg/m2 IV

Repeat cycle every 4 weeks for 4 cycles.

Carboplatin + paclitaxel25,c

Day 1: Paclitaxel 200mg/m2 IV + carboplatin AUC 6mg min/mL IV.

Repeat every 3 weeks until disease progression or unacceptable toxicity.

Docetaxel36,37,c

Day 1: Docetaxel 75mg/m2 IV over 1 hour.

Repeat cycle every 3 weeks.

Gemcitabine38-40

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

Repeat cycle every 3 weeks.

Gemcitabine + docetaxel30,c

Days 1 and 8: Gemcitabine 1,000mg/m2 IV

Day 8: Docetaxel 85mg/m2 IV.

Repeat cycle every 3 weeks for 8 cycles.

Gemcitabine + vinorelbine31

Days 1 and 8: Vinorelbine 25mg/m2 IV + gemcitabine 1,000mg/m2 IV.

Repeat cycle every 3 weeks.

Paclitaxel41-43

Days 1, 8, and 15: Paclitaxel 80mg/m2 IV.

Repeat cycle every 4 weeks for up to 4 cycles.

Maintenance Therapy for Advanced & Metastatic Disease1

Principles of Maintenance Therapy1

Continuation maintenance refers to the use of at least one of the agents given in first line, beyond 4 to 6 cycles, in the absence of disease progression. Switch maintenance refers to the initiation of a different agent, not included as part of the first-line regimen, in the absence of disease progression, after 4 to 6 cycles of initial therapy.

Continuation Maintenance: Bevacizumab and cetuximab given in combination with chemotherapy should be continued until evidence of disease progression or unacceptable toxicity, as per the design of the clinical trials supporting their use.

Continuation of bevacizumab after 4–6 cycles of platinum-doublet chemotherapy and bevacizumab (category 1).

Continuation of cetuximab after 4–6 cycles of cisplatin, vinorelbine, and cetuximab (category 1).

Continuation of pemetrexed after 4–6 cycles of cisplatin and pemetrexed chemotherapy, for patients with histologies other than squamous cell carcinoma (category 1).

Continuation of bevacizumab + pemetrexed after 4–6 cycles of bevacizumab, pemetrexed, cisplatin/carboplatin, for patients with histologies other than squamous cell carcinoma.

Continuation of gemcitabine after 4–6 cycles of platinum-doublet chemotherapy (category 2B).

Switch Maintenance: Two studies have shown a benefit in progression-free and overall survival with the initiation of pemetrexed after first-line chemotherapy, in patients without disease progression after 4–6 cycles of therapy.

Initiation of pemetrexed after 4–6 cycles of first-line platinum-doublet chemotherapy for patients with histologies other than squamous cell carcinoma (category 2B).

Initiation of docetaxel after 4–6 cycles of first-line platinum-doublet chemotherapy in patients with squamous cell carcinoma (category 2B).

Close surveillance of patients without therapy is a reasonable alternative to maintenance.

Subsequent Therapy for Advanced & Metastatic Disease1

Principles of Subsequent Therapy1

In patients who have experienced disease progression either during or after first-line therapy, single-agent docetaxel, or pemetrexed are established second-line agents.

Nivolumab improves survival when compared with docetaxel

Pembrolizumab improves overall survival in PD-L1 positive tumors when compared with docetaxel.

Docetaxel is superior to vinorelbine or ifosfamide.

Pemetrexed is considered equivalent to docetaxel with less toxicity in patients with adenocarcinoma and large cell carcinoma.

Ramucirumab + docetaxel improves survival when compared to docetaxel alone.

If not already given, options for patients with PS 0–2 include docetaxel, pemetrexed (nonsquamous), erlotinib, or gemcitabine (category 2B for all options).

Response assessment with CT of known sites with or without contrast every 6–12 weeks.

Nivolumab (Category 1)45,46

Day 1: Nivolumab 240mg IV over 60 minutes every 2 weeks until disease progression or unacceptable toxicity.

Pembrolizumab (Category 1)47,57,e,f

Day 1: Pembrolizumab 2mg/kg IV.

Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Atezolizumab (Category 1)48,65,f

Day 1: Atezolizumab 1200mg IV over 1 hour.

Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Docetaxel36,37

Day 1: Docetaxel 75mg/m2 IV over 1 hour.

Repeat cycle every 3 weeks.

Pemetrexed44

Day 1: Pemetrexed 500mg/m2 IV.

Repeat cycle every 3 weeks.

Gemcitabine38-40

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

Repeat cycle every 3 weeks.

Ramucirumab + docetaxel49

Day 1: Ramucirumab 10mg/kg IV + docetaxel 75mg/m2 IV.

Repeat cycle every 3 weeks.

First-line Targeted Therapy for Advanced & Metastatic Disease1

Sensitizing EGFR Mutation Positive1

Erlotinib (Category 1)58

Erlotinib 150mg orally once daily until disease progression or unacceptable toxicity.

Afatinib (Category 1)59

Afatinib 40mg orally once daily until disease progression or unacceptable toxicity.

Gefitinib (Category 1)60

Gefitinib 250mg orally once daily until disease progression or unacceptable toxicity.

ALK Positive1

Crizotinib (Category 1)56,61

Crizotinib 250mg orally twice daily until disease progression or unacceptable toxicity.

Alectinib (Category 1) Preferred52,53,64

Day 1: Alectinib 600mg orally twice daily.

Repeat until disease progression or unacceptable toxicity.

Ceritinib (Category 1)54,55,63

Day 1: Ceritinib 750mg orally once daily.

Repeat until disease progression or unacceptable toxicity.

ROS1 Rearrangemnt Poesitive1

Crizotinib56,61

Day 1: Crizotinib 250mg orally twice daily.

Repeat until disease progression or unacceptable toxicity.

BRAF V600E Mutation Positive1

Dabrafenib + trametinib50,68,69,g

Day 1: Dabrafenib 150mg orally twice daily

Day 1: Trametinib 2mg orally once daily

Repeat until disease progression or unacceptable toxicity.

See First-line therapy options for adenocarcinoma/squamous cell carcinoma.

PD-L1 Expression Positive1

Pembrolizumab (Category 1)51,e

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks until disease progression or unacceptable toxicity

Subsequent Targeted Therapy for Advanced & Metastatic Disease1

Sensitizing EGFR Mutation Positive1,h

Osimertinib (Category 1)62,i

Osimertinib 80mg orally once daily until disease progression or unacceptable toxicity.

Erlotinib58

Erlotinib 150mg orally once daily until disease progression or unacceptable toxicity.

Afatinib59

Afatinib 40mg orally once daily until disease progression or unacceptable toxicity.

Gefitinib60

Gefitinib 250mg orally once daily until disease progression or unacceptable toxicity.

ALK Positive1

Crizotinib56,61

Crizotinib 250mg orally twice daily until disease progression or unacceptable toxicity.

Ceritinib54,55,63

Ceritinib 750mg orally once daily until disease progression or unacceptable toxicity.

Alectinib52,53,64

Alectinib 600mg orally twice daily until disease progression or unacceptable toxicity.

Brigatinib67

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

Day 1: Brigatinib 180mg orally once daily

Repeat until disease progression or unacceptable toxicity.

Refer to guidelines.

ROS1 Rearrangement Positive1

See first-line therapy options for adenocarcinoma, squamous cell carcinoma, or PD-L1 expression positive (>50%)

BRAF V600E Mutation Positive1

If progression occurs after dabrafenib + trametinib, recommendation is first-line therapy options for adenocarcinoma/squamous cell carcinoma.

If progression occurs after first-line therapy options for adenocarcinoma/squamous cell carcinoma, recommendation is dabrafenib + trametinib.

PD-L1 Expression Positive1

See first-line therapy options for adenocarcinoma or squamous cell carcinoma

a Regimens can be used as neoadjuvant/preoperative/induction chemoradiotherapy.

b Regimens can be used as adjuvant or definitive concurrent chemotherapy/RT.

c 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.

d Bevacizumab should be given until progression.

e Pembrolizumab is approved for patients with NSCLC with PD-L1 expression levels >1%, as determined by an FDA-approved test.

f If pembrolizumab not previously given.

g Single-agent vemurafenib or dabrafenib are treatment options if the combination of dabrafenib + trametinib is not tolerated.

h T790M testing should be performed upon progression.

i Osimertinib if T790M(+) disease, if T790M(-) refer to first line therapy options for adenocarcinoma, squamous cell carcinoma, or PD-L1 expression positive (>50%). Refer to Treatment Guidelines.

References

1. Referenced with permission from NCCN Clinical Practice Guidelines in Oncology™ Non-Small Cell Lung Cancer. v 9.2017. Available at: http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed October 3, 2017.

2. Winton T, Livingston R, Johnson D, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-lung cancer. N Engl J Med. 2005;352:2589–2597.

3. Arriagada R, Bergman B, Dunant A, et al. The International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small cell lung cancer. N Engl J Med. 2004;350:351–360.

4. 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.

5. 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-cell lung cancer. J Clin Oncol. 2012;30:3516–3524.

6. 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.

7. Kreuter M, Vansteenkiste J, Fishcer 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.

8. Strauss GM, Herndon III JE, 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.

9. Albain KS, Crowley JJ, Turrisi AT III, 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.

10. Curran WJ Jr, Paulus R, Langer CJ, et al. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011;103:1452–1460.

11. 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.

12. 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 e systematic review of completed and ongoing studies. Lung Cancer. 2015;87:232–240.

13. Senan S, Brade A, Wang LH, et al. PROCLAIM: randomized phase III trial of pemetrexed-cisplatin or etoposide-cisplatin plus thoracic radiation therapy followed by consolidation chemotherapy in locally advanced nonsquamous non-small-cell lung cancer. J Clin Oncol. 2016;34:953–962.

14. Bradley JD, Paulus R, Komaki 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;16:187–199.

15. 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.

16. Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after chemoradiotherapy in stage III non-small cell lung cancer [article and supplementary appendix published online ahead of print September 8, 2017]. N Engl J Med. 2017.

17. 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.

18. 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.

19. Barlesi F, Scherpereel A, Rittmeywr 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. J Clin Oncol. 2013;31:3004–3011.

20. 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.

21. Fossella F, Periera 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(16):3016–3024.

22. 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.

23. Frasci G, Comella P, Panza N, eta l. 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.

24. 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 ciplatin in patients with advanced non-small-cell lung carcinoma. Cancer. 2003;98:542–553.

25. 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.

26. 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.

27. Cardenal F, Lopez-Cabrerizo MP, Anton 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.

28. 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 NSCLC. J Clin Oncol. 2008;26:3543–3551.

29. 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.

30. 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.

31. 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.

32. Langer CJ, 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.

33. Green M, Manikhas G, 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.

34. Rizvi N, Riely G, Azzoli, C, 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.

35. 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.

36. 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.

37. 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.

38. 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.

39. 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;23:8380–8288.

40. Perol M, Chouaid C, Perol 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 cell lung cancer. J Clin Oncol. 2012;30:3516–3524.

41. Lilenbaum RC, Herndon JE, 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.

42. 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.

43. 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.

44. Hanna NH, Sheperd FA, Fossella FV, et al. Randomized phase III study of pemetrexed versus docetaxel in patients with non-small cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004;22:1589–1597.

45. 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.

46. 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.

47. Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2015.

48. Barlesi F, Park K, Ciardiello F, et al. Primary analysis from OAK, a randomized phase III study comparing atezolizumab with docetaxel in 2L/3L NSCLC [abstract]. ESMO Congress; Copenhagen. ESMO 2016: LBA44.

49. 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.

50. Planchard D, Besse B, Groen HJM, et al. An open-label phase 2 trial of dabrafenib plus trametinib in patients with previously treated BRAF V600E-mutant metastatic non-small cell lung cancer. Lancet Oncol. 2016;17:984–993.

51. Reck M, Rodriguez-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.

52. 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(7):661–668.

53. Shaw AT, Gandhi L, Gadgeel S, et al. Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial. Lancet Oncol. 2016;17(2):234-242.

54. Shaw AT, Kim DW, Mehra R, et al. Ceritinib in ALK-Rearranged Non–Small-Cell Lung Cancer. N Engl J Med. 2014;370(13):1189–97.

55. 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(10072):917–929.

56. Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363(18):1693–703.

57. Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the Treatment of Non–Small-Cell Lung Cancer, N Engl J Med. 2015;372(21):2018–28.

58. Tarceva [prescribing information]. South San Francisco, CA: Genentech, Inc.; 2016

59. Gilotrif [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2016.

60. Iressa [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals; 2015.

61. Xalkori [prescribing information]. New York, NY: Pfizer Inc.; 2016.

62. Tagrisso [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals; 2016.

63. Zykadia [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals; 2016.

64. Alecensa [prescribing information]. South San Francisco, CA: Genentech, Inc.; 2016.

65. Tecentriq [prescribing information]. South San Francisco, CA: Genentech, Inc.; 2017.

66. Keytruda [prescribing information]. Whitehouse Station, NJ: Merck & Co, Inc.; 2017.

67. Alunbrig [prescribing information]. Cambridge, MA: Ariad Pharmaceuticals, Inc.; 2017.

68. Tafinlar [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; 2015.

69. Mekinist [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; 2015.


Lung Cancer Drug Monographs

Respiratory And Thoracic Cancers

ABRAXANE ALECENSA ALIMTA
AVASTIN BLEOMYCIN CYRAMZA
DOXORUBICIN HCL DOXORUBICIN HCL SOLUTION ETOPOPHOS
ETOPOSIDE CAPSULES GEMZAR GILOTRIF
HYCAMTIN HYCAMTIN CAPSULES IRESSA
KEYTRUDA METHOTREXATE FOR INJECTION METHOTREXATE INJECTION
MUSTARGEN NAVELBINE OPDIVO
PHOTOFRIN PORTRAZZA TAGRISSO
TARCEVA TAXOL TAXOTERE
TECENTRIQ TOPOSAR TREXALL
XALKORI ZYKADIA

Data provided by the Monthly Prescribing Reference (MPR) Hematology/Oncology Edition.

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