Non-Small Cell Lung Cancer Treatment Regimens

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NON-SMALL CELL LUNG CANCER TREATMENT REGIMENS

10/2016

© 2016 Haymarket Media, Inc.

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 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 non-small cell lung cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These non-small cell lung cancer treatment regimens are provided only to supplement the latest treatment strategies.

These Cancer Treatment 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 National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

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 + carboplatin9

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/RT1ab

Cisplatin + etoposide9,10

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

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

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

Day 1: Cisplatin 75 mg/m2 IV.

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

Repeat every 3 weeks for 3 cycles.

Paclitaxel + carboplatin13

Paclitaxel 45mg/m2 IV + carboplatin AUC 2mg min/mL IV weekly with concurrent thoracic radiotherapy (total dose, 60Gy) given 5 days per weeks in 2Gy fractions.

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 + carboplatin14

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.

Concurrent Chemotherapy/RT Followed by Chemotherapy1

Paclitaxel + carboplatin14

Day 1 (weekly): Paclitaxel 45–50mg/m2 IV and carboplatin AUC 2mg min/mL IV.

Concurrent thoracic radiotherapy; followed by 2 additional cycles of paclitaxel 200mg/m2 IV and carboplatin AUC 6mg min/mL IV.

Cisplatin + etoposide10

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

Days 1–5, 29–33: Etoposide 50mg/m2 IV with concurrent thoracic radiotherapy; followed by 2 additional cycles of cisplatin 50mg/m2 IV and etoposide 50mg/m2 IV.

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 1–2 cycles, then every 2–4 cycles.

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

Bevacizumab + carboplatin + paclitaxel (Category 1)15

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 + pemetrexed16

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 + pemetrexed17

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)18

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)19c

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)20,21

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)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)23c

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)24

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

Repeat cycle every 3 weeks for up to 6 cycles.

Carboplatin + vinorelbine (Category 1)25

Day 1: Carboplatin AUC 6mg min/mL IV

Days 1 and 8: Vinorelbine 30mg/m2 IV

Day 9: Pegfilgrastim 6mg SC.

Repeat cycle every 3 weeks for 4 cycles.

Cisplatin + docetaxel (Category 1)19c

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

Repeat cycle every 3 weeks.

Cisplatin + etoposide (Category 1)26

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)23,27

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)28c

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

Day 2: Cisplatin 75mg/m2 IV.

Repeat cycle every 3 weeks.

Cisplatin + pemetrexed (Category 1)27

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

Repeat cycle every 3 weeks.

Cisplatin + vinorelbine (Category 1)19,23,29

Day 1: Cisplatin 100mg/m2 IV

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

Repeat cycle every 4 weeks.

Gemcitabine + docetaxel (Category 1)30c

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.

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

Albumin-bound paclitaxel32

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

Repeat cycle every 3 weeks.

Carboplatin + albumin-bound paclitaxel33,34

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 + docetaxel19c

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

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

Carboplatin + etoposide20,21

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 + gemcitabine22

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 + paclitaxel23c

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

Repeat every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + pemetrexed24

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

Repeat cycle every 3 weeks for up to 6 cycles.

Carboplatin + vinorelbine25

Day 1: Carboplatin AUC 6mg min/mL IV

Days 1 and 8: Vinorelbine 30mg/m2 IV

Day 9: Pegfilgrastim 6mg SC.

Repeat cycle every 3 weeks for 4 cycles.

Docetaxel35,36c

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

Repeat cycle every 3 weeks.

Etoposide37

Days 1–21: Etoposide 50mg/m2 orally daily.

Repeat cycle every 4 to 5 weeks.

Gemcitabine38-40

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

Repeat cycle every 3 weeks.

Gemcitabine + docetaxel30c

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.

Irinotecan41,42

Day 1: Irinotecan 300mg/m2 IV.

Repeat cycle every 3 weeks.

Paclitaxel43-45

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

Repeat cycle every 4 weeks for up to 4 cycles.

Pemetrexed46

Day 1: Pemetrexed 500mg/m2 IV.

Repeat cycle every 3 weeks.

Vinorelbine35

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

Repeat cycle every 3 weeks.

Squamous Cell Carcinoma (PS 0-1)1

Carboplatin + albumin-bound paclitaxel (Category 1)18

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)19

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)20,21

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 + 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)23c

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

Repeat every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + vinorelbine (Category 1)25

Day 1: Carboplatin AUC 6mg min/mL IV

Days 1 and 8: Vinorelbine 30mg/m2 IV

Day 9: Pegfilgrastim 6mg SC.

Repeat cycle every 3 weeks for 4 cycles.

Cisplatin + docetaxel (Category 1)19

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

Repeat cycle every 3 weeks.

Cisplatin + etoposide (Category 1)26

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)23,27

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)28c

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

Day 2: Cisplatin 75mg/m2 IV.

Repeat cycle every 3 weeks.

Cisplatin + vinorelbine (Category 1)19,23,29

Day 1: Cisplatin 100mg/m2 IV

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

Repeat cycle every 4 weeks.

Cisplatin + gemcitabine + necitumumab (Category 3)47

Day 1: Cisplatin 75mg/m2 IV over 120 minutes

Days 1 and 8: Gemcitabine 1,250mg/m2 IV over 30 minutes + necitumumab 800mg IV over a minimum of 50 minutes.

Repeat cycle every 3 weeks for up to 6 cycles. Patients free of disease progression should continue single-agent necitumumab on the same treatment schedule until disease progression or unacceptable toxicity.

Gemcitabine + docetaxel (Category 1)30c

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 paclitaxel32

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

Repeat cycle every 3 weeks.

Carboplatin + albumin-bound paclitaxel33,34

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 + docetaxel19c

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

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

Carboplatin + etoposide20,21

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 + gemcitabine22

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 + paclitaxel23c

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

Repeat every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + vinorelbine24

Day 1: Carboplatin AUC 6mg min/mL IV

Days 1 and 8: Vinorelbine 30mg/m2 IV

Day 9: Pegfilgrastim 6mg SC.

Repeat cycle every 3 weeks for 4 cycles.

Cisplatin + gemcitabine + necitumumab (Category 3)47

Day 1: Cisplatin 75mg/m2 IV over 120 minutes

Days 1 and 8: Gemcitabine 1,250mg/m2 IV over 30 minutes + necitumumab 800mg IV over a minimum of 50 minutes.

Repeat cycle every 3 weeks for up to 6 cycles. Patients free of disease progression should continue single-agent necitumumab on the same treatment schedule until disease progression or unacceptable toxicity.

Docetaxel35,36c

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

Repeat cycle every 3 weeks.

Etoposide37

Days 1–21: Etoposide 50mg/m2 orally daily.

Repeat cycle every 4 to 5 weeks.

Gemcitabine38-40

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

Repeat cycle every 3 weeks.

Gemcitabine + docetaxel30c

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.

Irinotecan41,42

Day 1: Irinotecan 300mg/m2 IV.

Repeat cycle every 3 weeks.

Paclitaxel43-45

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

Repeat cycle every 4 weeks for up to 4 cycles.

Vinorelbine35

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

Repeat cycle every 3 weeks.

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 or erlotinib after first-line chemotherapy, in patients without disease progression after 4–6 cycles of therapy./p>

> 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 erlotinib after 4–6 cycles of first-line platinum-doublet chemotherapy (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, pemetrexed, or erlotinib 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.

> Erlotinib is superior to best supportive care.

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

Nivolumab (Category 1)48,49

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

Pembrolizumab (Category 1)50d

Day 1: Pembrolizumab 2mg/kg IV.

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

Docetaxel35,36

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

Repeat cycle every 3 weeks.

Pemetrexed46

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 + docetaxel51

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)52

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

Afatinib (Category 1)53

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

Gefitinib (Category 1)54

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

ALK Positive1

Crizotinib (Category 1)55

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

Subsequent Targeted Therapy for Advanced & Metastatic Disease1

Sensitizing EGFR Mutation Positive1

Osimertinib56

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

Erlotinib52

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

Afatinib53

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

Gefitinib54

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

ALK Positive1

Crizotinib55

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

Ceritinib57

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

Alectinib58

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

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

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 Pembrolizumab is approved for patients with NSCLC tumors with PD-L1 expression, as determined by an FDA-approved test for PD-L1 with use of pembrolizumab.

References

1. Referenced with permission from NCCN Clinical Practice Guidelines in Oncology™ Non-Small Cell Lung Cancer. v 4.2016. Available at: http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed September 15, 2016.

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.

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

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

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

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

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

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

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


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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