THIS SITE IS INTENDED FOR U.S. AUDIENCES ONLY.

Celgene

ADVANCED NSCLC DISEASE LANDSCAPEADVANCED NSCLC DISEASE LANDSCAPE

24% of patients receiving first-line therapy for advanced NSCLC have squamous histology1a
Percent distribution of stage IIIB-IV NSCLC patients receiving first-line therapy by histology1a
non-small cell lung cancer histology pie chart non-small cell lung cancer histology pie chart
  • aEstimates based on Kantar Health Patient Metrics; 2014.
  • bOther includes large cell carcinoma, non–small cell carcinoma, other specified carcinomas.
Patients with advanced squamous NSCLC are in urgent need of options that deliver tumor response
advanced squamous non-small cell lung cancer lung advanced squamous non-small cell lung cancer lung
Squamous cell carcinoma:
  • Associated with a poorer prognosis than nonsquamous2
  • Tumors are often centrally located3,4
  • Have been shown to grow twice as fast as adenocarcinoma5,6
  • Often seen extrinsically pushing into airway structures as they grow7
  • Associated with a history of smoking3
  • Importance of Tumor Response Rates

    RESPONSE RATES

    ARE HELPFUL IN ASSESSING CLINICAL BENEFIT
    ORR is a clinically meaningful end point in NSCLC trials that can help physicians choose an appropriate treatment8
    Using ORR as an end point in oncology drug approval has a long history
    There has been more than 30 years of experience with response criteria9

    ORR= overall response rate.

    CLOSE THE TAB
  • Measurement of Tumor Response

    TUMOR RESPONSE

    IS A RIGOROUS MEASUREMENT8
    Spatial measurement of tumor shrinkage is a form of direct, real-­time clinical assessment8

    Measure of the greater unidimensional diameters

    RECIST Criteria6

    CR=complete response

    PR=partial response

    SD=stable disease

    PD=progressive disease

    CR

    Disappearance of all clinical and radiological evidence of target lesions

    PR

    ≥30% decrease of the greater unidimensional diameters

    SD

    Failure to observe CR or PR, but not PD

    PD

    ≥20% increase of the greater unidimensional diameters or presence of new lesion

    Measure of the greater
    unidimensional
    diameters

    Complete Response (CR)

    Disappearance of all clinical and radiological evidence of target lesions

    Partial Response (PR)

    ≥30% decrease of the greater unidimensional diameters

    Stable Disease (SD)

    Failure to observe CR or PR, but not PD

    Progressive Disease (PD)

    ≥20% increase of the greater unidimensional diameters or presence of new lesion

    Response assessment under RECIST guidelines is based on measurement of the longest single-dimension diameters of target lesions, which are identified at baseline.

    CLOSE THE TAB
THE ABRAXANE PIVOTAL PHASE III TRIAL INCLUDED OVER 1000 PATIENTS

WITH ADVANCED SQUAMOUS AND NONSQUAMOUS NSCLC

non-small cell lung cancer trial design non-small cell lung cancer trial design

Treatment administered until disease progression or development of unacceptable toxicity

*First-line ABRAXANE + carboplatin has not been studied in chemonaïve patients who have progressed on initial immunotherapy.


Studied in a broad range of chemonaïve patients with advanced NSCLC
Studied in a broad range of chemonaïve patients with advanced NSCLC
Stratified by histologies and age10,11

ABRAXANE + carboplatin arm (n=521)

non-small cell lung cancer study patient population pie chart non-small cell lung cancer study patient population pie chart
Three-quarters of the patients had a history of smoking10
Three-quarters of the patients
had a history of smoking10

ABRAXANE + carboplatin arm (n=519)a

non-small cell lung cancer study patient population smoking non-small cell lung cancer study patient population smoking
  • aThe was unknown for 2 patients in the ABRAXANE + carboplatin arm.

ESTABLISHED SAFETY PROFILE

IN ADVANCED NSCLC
Selected ARs with a difference of ≥5% for all grades or ≥2% for Grade 3-4 toxicity between treatment groups
non-small cell lung cancer established safety profile chart non-small cell lung cancer established safety profile chart
  • a508 patients assessed in ABRAXANE/carboplatin-treated group.
  • b514 patients assessed in paclitaxel injection/carboplatin-treated group.
  • c513 patients assessed in paclitaxel injection/carboplatin-treated group.
  • dPeripheral neuropathy is defined by the MedDRA v14.0 SMQ neuropathy (broad scope).
  • MedDRA=Medical Dictionary for Regulatory Activities; SMQ=Standardized MedDRA Query.
  • a508 patients assessed in ABRAXANE/carboplatin-treated group.
  • b514 patients assessed in paclitaxel injection/carboplatin-treated group.
  • c513 patients assessed in paclitaxel injection/carboplatin-treated group.
  • dPeripheral neuropathy is defined by the MedDRA v14.0 SMQ neuropathy (broad scope).
  • MedDRA=Medical Dictionary for Regulatory Activities; SMQ=Standardized MedDRA Query.
  • Most Common Adverse Reactions

    ESTABLISHED SAFETY PROFILE

    IN ADVANCED NSCLC
    Common ARs (≥10%) for ABRAXANE + carboplatin observed at a similar incidence as with paclitaxel injection + carboplatin
    Common ARs (≥10%) for ABRAXANE + carboplatin observed at a similar incidence as with paclitaxel injection + carboplatin
    non-small cell lung cancer established safety profile adverse reactions chart non-small cell lung cancer established safety profile adverse reactions chart
    CLOSE THE TAB
NCCN CLINICAL PRACTICE GUIDELINES IN ONCOLOGY (NCCN GUIDELINES®)

CATEGORY 1 RECOMMENDATION

non-small cell lung cancer nccn guidelinesnon-small cell lung cancer nccn guidelines
  • aFor additional considerations and treatment options, see NCCN.org.
  • bEGFR, ALK, ROS-1, and PD-L1 negative or unknown.
  • The NCCN Guidelines® are a work in progress that may be refined as often as new significant data becomes available. The NCCN Guidelines® are a statement of consensus 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.
ABRAXANE IS ADMINISTERED WEEKLY OVER 30 MINUTES

GENERALLY WITHOUT THE NEED FOR STEROID PRETREATMENT

Premedication may be needed in patients who have had a prior hypersensitivity reaction to ABRAXANE
  • Severe hypersensitivity reactions with fatal outcome have been reported with ABRAXANE. Do not re-challenge
  • Severe hypersensitivity reactions with fatal outcome have been reported with ABRAXANE.
    Do not re-challenge

Administer ABRAXANE intravenously at
a dose of 100 mg/m2

Administer ABRAXANE intravenously at a dose of
100 mg/m2

non-small cell lung cancer dosing bottles 100 + 6 non-small cell lung cancer dosing bottles 100 + 6
ILLUSTRATIVE PURPOSES ONLY

The recommended ABRAXANE schedule is weekly dosing

The recommended ABRAXANE schedule is weekly dosing

non-small cell lung cancer weekly dosing non-small cell lung cancer weekly dosing
  • Administer ABRAXANE on Days 1, 8, and 15 of each 21-day cycle
  • Administer carboplatin on Day 1 of each 21-day cycle

ABRAXANE is administered
over 30 minutes

ABRAXANE is administered
over 30 minutes

non-small cell lung cancer 30 minute administration non-small cell lung cancer 30 minute administration

Note: An albumin form of paclitaxel may substantially affect a drug’s functional properties relative to those of drug in solution. DO NOT SUBSTITUTE FOR OR WITH OTHER PACLITAXEL FORMULATIONS.

  • Duration and Dosing in the
    Phase III Trial

    MEDIAN NUMBER OF TREATMENT CYCLES

    MEDIAN NUMBER OF TREATMENT CYCLES

    IN THE PHASE III PIVOTAL TRIAL OF ABRAXANE + CARBOPLATIN
    non-small cell lung cancer 6 median cycles non-small cell lung cancer 6 median cycles
    Patients in the study were treated until disease progression or development of unacceptable toxicity. 

    DOSE ADJUSTMENTS

    DOSE ADJUSTMENTS

    OBSERVED IN THE PHASE III PIVOTAL TRIAL
    Adverse reactions were assessed in 514 patients treated with ABRAXANE + carboplatin
    non-small cell lung cancer dose adjustments non-small cell lung cancer dose adjustments
    CLOSE THE TAB
  • Dose Modifications
    PLEASE SELECT A DOSE MODIFICATION BELOW:
    • Hepatic

      START WITH THE RIGHT DOSE

      IN PATIENTS WITH HEPATIC IMPAIRMENT

      START WITH THE RIGHT DOSE

      IN PATIENTS WITH HEPATIC IMPAIRMENT
      Recommendations for starting dose in patients with hepatic impairment
      SGOT (AST) LEVELS
      <10 x ULN
      SGOT (AST) LEVELS <10 x ULN
      AND
      BILIRUBIN LEVELS
      >ULN TO ≤1.5 x ULN
      BILIRUBIN LEVELS >ULN TO ≤1.5 x ULN
      SGOT (AST) LEVELS
      <10 x ULN
      SGOT (AST) LEVELS <10 x ULN
      AND
      BILIRUBIN LEVELS
      >1.5 TO ≤3 x ULN
      BILIRUBIN LEVELS >1.5 TO ≤3 x ULN
      SGOT (AST) LEVELS
      <10 x ULN
      SGOT (AST) LEVELS <10 x ULN
      AND
      BILIRUBIN LEVELS
      >3 TO ≤5 x ULN
      BILIRUBIN LEVELS >3 TO ≤5 x ULN
      SGOT (AST) LEVELS
      >10 x ULN
      SGOT (AST) LEVELS >10 x ULN
      OR
      BILIRUBIN LEVELS
      >5 x ULN
      BILIRUBIN LEVELS >5 x ULN

      Mild

      • No dose adjustment is necessary for patients with mild hepatic impairment
      • Do not administer ABRAXANE to patients with total bilirubin >5 x ULN or AST >10 x ULN
      • Patients with bilirubin levels above the ULN were excluded from the clinical trial for lung cancer 
      • Dosage recommendations are for the first course of therapy. The need for further dose adjustments in subsequent courses should be based on individual tolerance
      • Patients with bilirubin levels above the ULN were excluded from the clinical trial for lung cancer 
      • Dosage recommendations are for the first course of therapy. The need for further dose adjustments in subsequent courses should be based on individual tolerance

      Moderate

      • Do not administer ABRAXANE to patients with total bilirubin >5 x ULN or AST >10 x ULN 
      • Patients with bilirubin levels above the ULN were excluded from the clinical trial for lung cancer 
      • Dosage recommendations are for the first course of therapy. The need for further dose adjustments in subsequent courses should be based on individual tolerance

      Severe

      • Do not administer ABRAXANE to patients with total bilirubin >5 x ULN or AST >10 x ULN 
      • Patients with bilirubin levels above the ULN were excluded from the clinical trial for lung cancer 
      • Dosage recommendations are for the first course of therapy. The need for further dose adjustments in subsequent courses should be based on individual tolerance

      Very Severe

      • Do not administer ABRAXANE to patients with total bilirubin >5 x ULN or AST >10 x ULN 
      • Patients with bilirubin levels above the ULN were excluded from the clinical trial for lung cancer 
      ULN=upper limit of normal.

      ABRAXANE dose

      non-small cell lung cancer dosing bottles 100 non-small cell lung cancer dosing bottles 80 non-small cell lung cancer dosing bottles 80 non-small cell lung cancer dosing bottles not recommended

      ILLUSTRATIVE PURPOSES ONLY

      • aA dose increase to 100 mg/m2 in subsequent courses should be considered if the patient tolerates the reduced dose for 2 cycles.
    • Neutropenia

      DOSING FOR YOUR PATIENTS

      WHO EXPERIENCE HEMATOLOGIC TOXICITIES

      DOSING FOR YOUR PATIENTS

      WHO EXPERIENCE HEMATOLOGIC TOXICITIES
      Recommendations for permanent dose modification in NSCLC patients with neutropenia
      MAKE A SELECTION:

      • Nadir ANC <500 cells/mm3 with neutropenic fever >38OC
      OR
      • Delay of next cycle due to persistent neutropenia* (nadir ANC <1500 cells/mm3)
      OR
      • Nadir ANC <500 cells/mm3 for >1 week
      • Prior to permanent dose reduction, withhold treatment until ANC recovery to ≥1500 cells/mm3 on Day 1 or ≥500 cells/mm3 on Day 8 or 15 of a cycle
      • Nadir ANC <500 cells/mm3 with neutropenic fever >38OC
      OR
      • Delay of next cycle due to persistent neutropenia*
        (nadir ANC <1500 cells/mm3)
      OR
      • Nadir ANC <500 cells/mm3 for >1 week
      • Prior to permanent dose reduction, withhold treatment until ANC recovery to ≥1500 cells/mm3 on Day 1 or ≥500 cells/mm3 on Day 8 or 15 of a cycle
      • Nadir ANC <500 cells/mm3 with neutropenic fever >38OC
      OR
      • Delay of next cycle due to persistent neutropenia*
        (nadir ANC <1500 cells/mm3)
      OR
      • Nadir ANC <500 cells/mm3 for >1 week
      • Prior to permanent dose reduction, withhold treatment until ANC recovery to ≥1500 cells/mm3 on Day 1 or ≥500 cells/mm3 on Day 8 or 15 of a cycle

       

      non-small cell lung cancer dosing bottles 75 + 4.5 non-small cell lung cancer dosing bottles 50 + 3 non-small cell lung cancer dosing bottles discontinue treatment

      ILLUSTRATIVE PURPOSES ONLY

      • Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to dosing on Days 1, 8, and 15
      • In the phase III ABRAXANE NSCLC clinical trial, 85% of patients treated with ABRAXANE (100 mg/m2 weekly) + carboplatin experienced Grade 1-4 neutropenia; 47% experienced
        Grade 3-4 neutropenia
      • Do not administer ABRAXANE on Day 1 of a cycle until absolute neutrophil count (ANC) is at least 1500 cells/mm3 and platelet count is at least 100,000 cells/mm3
      • Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to dosing on Days 1, 8, and 15
      • In the phase III ABRAXANE NSCLC clinical trial, 85% of patients treated with ABRAXANE (100 mg/m2 weekly) + carboplatin experienced Grade 1-4 neutropenia; 47% experienced Grade 3-4 neutropenia
      • Do not administer ABRAXANE on Day 1 of a cycle until absolute neutrophil count (ANC) is at least 1500 cells/mm3 and platelet count is at least 100,000 cells/mm3
      • Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to dosing on Days 1, 8, and 15
      • In the phase III ABRAXANE NSCLC clinical trial, 85% of patients treated with ABRAXANE (100 mg/m2 weekly) + carboplatin experienced Grade 1-4 neutropenia; 47% experienced
        Grade 3-4 neutropenia
      • Do not administer ABRAXANE on Day 1 of a cycle until absolute neutrophil count (ANC) is at least 1500 cells/mm3 and platelet count is at least 100,000 cells/mm3
      • Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to dosing on Days 1, 8, and 15
      • In the phase III ABRAXANE NSCLC clinical trial, 85% of patients treated with ABRAXANE (100 mg/m2 weekly) + carboplatin experienced Grade 1-4 neutropenia; 47% experienced Grade 3-4 neutropenia
      • Do not administer ABRAXANE on Day 1 of a cycle until absolute neutrophil count (ANC) is at least 1500 cells/mm3 and platelet count is at least 100,000 cells/mm3
      • Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to dosing on Days 1, 8, and 15
      • In the phase III ABRAXANE NSCLC clinical trial, 85% of patients treated with ABRAXANE (100 mg/m2 weekly) + carboplatin experienced Grade 1-4 neutropenia; 47% experienced
        Grade 3-4 neutropenia
      • Do not administer ABRAXANE on Day 1 of a cycle until absolute neutrophil count (ANC) is at least 1500 cells/mm3 and platelet count is at least 100,000 cells/mm3
      • Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to dosing on Days 1, 8, and 15
      • In the phase III ABRAXANE NSCLC clinical trial, 85% of patients treated with ABRAXANE (100 mg/m2 weekly) + carboplatin experienced Grade 1-4 neutropenia; 47% experienced Grade 3-4 neutropenia
      • Do not administer ABRAXANE on Day 1 of a cycle until absolute neutrophil count (ANC) is at least 1500 cells/mm3 and platelet count is at least 100,000 cells/mm3
      • *Maximum of 7 days post-scheduled Day 1 dose of next cycle.
    • Thrombocytopenia

      DOSING FOR YOUR PATIENTS

      WHO EXPERIENCE HEMATOLOGIC TOXICITIES

      DOSING FOR YOUR PATIENTS

      WHO EXPERIENCE HEMATOLOGIC TOXICITIES
      Recommendations for permanent dose modification in NSCLC patients with thrombocytopenia
      MAKE A SELECTION:

      • Prior to permanent dose reduction, withhold treatment until platelet count recovery to ≥100,000 cells/mm3 on Day 1 or ≥50,000 cells/mm3 on Days 8 or 15 of the cycle
      • Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to dosing on Days 1, 8, and 15
      • In the phase III ABRAXANE NSCLC clinical trial, 68% of patients treated with ABRAXANE (100 mg/m2 weekly) + carboplatin experienced Grade 1-4 thrombocytopenia; 18% experienced Grade 3-4 thrombocytopenia
      • Do not administer ABRAXANE on Day 1 of a cycle until absolute neutrophil count (ANC) is at least 1500 cells/mm3 and platelet count is at least 100,000 cells/mm3
      • Prior to permanent dose reduction, withhold treatment until platelet count recovery to ≥100,000 cells/mm3 on Day 1 or ≥50,000 cells/mm3 on Days 8 or 15 of the cycle
      • Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to dosing on Days 1, 8, and 15
      • In the phase III ABRAXANE NSCLC clinical trial, 68% of patients treated with ABRAXANE (100 mg/m2 weekly) + carboplatin experienced Grade 1-4 thrombocytopenia; 18% experienced Grade 3-4 thrombocytopenia
      • Do not administer ABRAXANE on Day 1 of a cycle until absolute neutrophil count (ANC) is at least 1500 cells/mm3 and platelet count is at least 100,000 cells/mm3

      Nadir platelets <50,000 cells/mm3

      non-small cell lung cancer dosing bottles 75 + 4.5 non-small cell lung cancer dosing bottles discontinue treatment

      ILLUSTRATIVE PURPOSES ONLY

    • Neurologic

      DOSING FOR YOUR PATIENTS

      WHO EXPERIENCE NEUROLOGIC TOXICITIES

      DOSING FOR YOUR PATIENTS

      WHO EXPERIENCE NEUROLOGIC TOXICITIES
      Recommendations for permanent dose modification in NSCLC patients with neurologic toxicity
      MAKE A SELECTION:

      • For Grade 3-4 peripheral neuropathy, withhold treatment until resolution to ≤Grade 1
        • Treatment may be resumed at the next lower dose level in subsequent cycles according to the dose reduction guidelines for neurologic toxicity
      • In the phase III ABRAXANE NSCLC clinical trial, 48% of patients treated with ABRAXANE (100 mg/m2 weekly) + carboplatin experienced Grade 1-4 peripheral neuropathy; 3% experienced Grade 3-4 peripheral neuropathy; no Grade 4 peripheral neuropathy was seen in the ABRAXANE + carboplatin arm
      • For Grade 3-4 peripheral neuropathy, withhold treatment until resolution to ≤Grade 1
        • Treatment may be resumed at the next lower dose level in subsequent cycles according to the dose reduction guidelines for neurologic toxicity
      • In the phase III ABRAXANE NSCLC clinical trial, 48% of patients treated with ABRAXANE (100 mg/m2 weekly) + carboplatin experienced Grade 1-4 peripheral neuropathy; 3% experienced Grade 3-4 peripheral neuropathy; no Grade 4 peripheral neuropathy was seen in the ABRAXANE + carboplatin arm
      • For Grade 3-4 peripheral neuropathy, withhold treatment until resolution to ≤Grade 1
        • Treatment may be resumed at the next lower dose level in subsequent cycles according to the dose reduction guidelines for neurologic toxicity
      • In the phase III ABRAXANE NSCLC clinical trial, 48% of patients treated with ABRAXANE (100 mg/m2 weekly) + carboplatin experienced Grade 1-4 peripheral neuropathy; 3% experienced Grade 3-4 peripheral neuropathy; no Grade 4 peripheral neuropathy was seen in the ABRAXANE + carboplatin arm

      Severe sensory neuropathy
      (Grade 3 or 4)

      non-small cell lung cancer dosing bottles 75 + 4.5 non-small cell lung cancer dosing bottles 50 + 3 non-small cell lung cancer dosing bottles discontinue treatment

      ILLUSTRATIVE PURPOSES ONLY

    CLOSE THE TAB
green brushstroke non-small cell lung cancer people non-small cell lung cancer sparkler

CHOOSE FIRST-LINE
ABRAXANE + CARBOPLATIN

FOR SQUAMOUS AND NONSQUAMOUS ADVANCED NSCLC

CHOOSE FIRST-LINE
ABRAXANE + CARBOPLATIN

FOR SQUAMOUS AND NONSQUAMOUS ADVANCED NSCLC

ORR IN THE ITT POPULATION

33%

(n=170/521)
(95% CI: 28.6%-36.7%)

VS

25%

(n=132/531)
(95% CI: 21.2%-28.5%)

P=0.005

ABRAXANE + carboplatin

Paclitaxel injection + carboplatin

  • Median duration of response was 6.9 months vs 6.0 months (95% CI: 5.6-8.0% vs 5.6-7.1%, respectively)
  • There was no statistically significant difference in overall survival (OS) between the 2 study arms (median OS 12.1 months vs 11.2 months, P=NS10)
  • Median duration of response was 6.9 months vs
    6.0 months (95% CI: 5.6-8.0% vs 5.6-7.1%, respectively)
  • There was no statistically significant difference in overall survival (OS) between the 2 study arms (median OS 12.1 months vs 11.2 months, P=NS10)

ABRAXANE + carboplatin

Paclitaxel injection + carboplatin

ORR IN PATIENTS WITH SQUAMOUS ADVANCED NSCLC

41%

(n=94/229)

VS

24%

(n=54/221)

ORR IN PATIENTS WITH NONSQUAMOUS ADVANCED NSCLC

Carcinoma/adenocarcinoma:

26%

(n=66/254)

VS

27%

(n=71/264)

Large cell carcinoma:

33%

(n=3/9)

VS

15%

(n=2/13)

Other forms of nonsquamous disease:

24%

(n=7/29)

VS

15%

(n=5/33)

ORR IN PATIENTS WITH SQUAMOUS ADVANCED NSCLC

41%

(n=94/229)

VS

24%

(n=54/221)

ORR IN PATIENTS WITH NONSQUAMOUS ADVANCED NSCLC

Carcinoma/adenocarcinoma:

26%

(n=66/254)

VS

27%

(n=71/264)

Large cell carcinoma:

33%

(n=3/9)

VS

15%

(n=2/13)

Other forms of nonsquamous disease:

24%

(n=7/29)

VS

15%

(n=5/33)

Study design

Multicenter, 1:1 randomized, phase III study comparing ABRAXANE (100 mg/m2 IV; Days 1, 8, and 15 of each 21-day cycle) + carboplatin (AUC=6 mg•min/mL IV, Day 1 of each 21-day cycle) with paclitaxel injection (200 mg/m2 IV, Day 1 of each 21-day cycle) + carboplatin (AUC=6 mg•min/mL IV, Day 1 of each 21-day cycle) in 1052 chemonaïve patients with NSCLC.

ITT=intent-to-treat; ORR=overall response rate.