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Celgene

PATIENTS WHO HAVE MBC WITH VISCERAL AND MULTIPLE METASTASES OFTEN HAVE LESS FAVORABLE OUTCOMES

Compared to those with nonvisceral metastases, patients with metastatic breast cancer who develop visceral metastases are likely to have a less favorable outcome1
metastatic breast cancer visceral metastases graphmetastatic breast cancer visceral metastases graph
There is lower median survival time for patients who develop visceral metastases vs nonvisceral metastases1c
  • aCharacteristics from a retrospective database analysis of 111 patients with primary breast cancer and concurrent distant metastases seen between 2005 and 2007.2
  • bCharacteristics from a retrospective review of 640 MBC patients who entered into 6 consecutive trials between 1983 and 2001.3
  • cUnivariate survival analysis from a retrospective database of 346 patients diagnosed with metastatic breast cancer after first recurrence between 1970 and 1991. All patients had undergone surgery for primary breast cancer and may have received radiation, hormonal therapy, and/or chemotherapy for metastatic disease.1
  • More Data on Visceral Metastases

    VISCERAL METASTASES

    A retrospective database analysis of 111 women at a single center in Canada between 2005-2007 found that about 67%-73% of patients with metastatic breast cancer developed visceral metastases.2 A retrospective analysis of 6 clinical studies between 1983-2001 (N=640) found that in 57%-74% of patients, visceral metastases developed as the dominant metastatic site.

    Further studies demonstrate that up to 85% of patients will develop visceral metastases at some point in the course of their disease.4-7

    Visceral metastases are associated with more aggressive metastatic breast cancer compared with nonvisceral metastases; patients tend to have worse outcomes.

    Visceral metastases are associated with more aggressive metastatic breast cancer1a
    metastatic breast cancer visceral vs nonvisceral metastases graphmetastatic breast cancer visceral vs nonvisceral metastases graph
    • aUnivariate survival analysis from a retrospective database of 346 patients with metastatic breast cancer after first recurrence. All patients had undergone surgery for primary breast cancer and may have received radiation, hormonal therapy, and/or chemotherapy for metastatic disease.
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  • More Detail on Multiple Metastases
    THE NUMBER OF METASTATIC SITES IS

    ASSOCIATED WITH MORE AGGRESSIVE MBC

    • The presence of multiple metastatic lesions or sites is associated with poor prognosis in patients with metastatic breast cancer8
    • Patients with metastatic breast cancer who present with metastases at ≥3 sites are likely to have a comparatively less favorable outcome than those with ≤2 metastatic sites9
    There is lower median survival time for patients with increasing number of metastatic sites9a
    metastatic breast cancer number of metastatic sites vs median survival graphmetastatic breast cancer number of metastatic sites vs median survival graph
    • aUnivariate survival analysis of 1430 patients from 8 consecutive prospective trials conducted between 1977 and 1992 of anthracycline-based first-line chemotherapy in metastatic breast cancer.
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A PHASE III TRIAL VS PACLITAXEL INJECTION

DESIGNED TO EVALUATE RESPONSE RATES IN MBC

metastatic breast cancer trial design metastatic breast cancer trial design
The majority of patients in both arms
had poor prognostic factors (N=454)
The majority of patients in both arms had poor prognostic factors (N=454)
metastatic breast cancer visceral vs nonvisceral metastases pie chart metastatic breast cancer visceral vs nonvisceral metastases pie chart
ECOG Performance Scores across both arms (N=454)10
ECOG Performance Scores across both arms (N=454)10
metastatic breast cancer study patient population pie chart metastatic breast cancer study patient population pie chart
  • A Rigorous Efficacy End Point

    PHASE III RIGOROUS TUMOR RESPONSE END POINT: recTLRR

    • The primary efficacy end point: Reconciled target lesion response rate (recTLRR)
      • recTLRR was based on independent radiologic assessment of tumor responses
      • recTLRR was reconciled with investigator-reported responses for the first 6 cycles of therapy
    • Secondary efficacy end points included time to disease progression and overall survival, among other measures11

    Patients who completed 6 cycles of ABRAXANE therapy and did not progress were able to continue treatment at the investigator’s discretion.11

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  • NCCN Recommendation
    RECOMMENDATIONS FOR MBC PATIENTS WITH

    VISCERAL METASTASES

    The predominance of visceral metastases in the Phase III study is consistent with the National Comprehensive Cancer Network® (NCCN) recommended patient population for albumin-bound paclitaxel (ABRAXANE)12

    *NCCN Guidelines (v1.2017) recommend albumin-bound paclitaxel as Category 2A.

    Please refer to the NCCN Drugs & Biologics Compendium® (NCCN Compendium®) entry for albumin-bound paclitaxel, revised March 2017. http://www.nccn.org

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  • Lines of Therapy

    PRIOR THERAPY

    IN A METASTATIC PATIENT POPULATION
    metastatic breast cancer study chemotherapy groups
    metastatic breast cancer second-line or later treatment graph

    ABRAXANE is indicated for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated.

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OBSERVED SAFETY PROFILE

ADVERSE EVENTS IN A PHASE III CLINICAL TRIAL
Frequencya of important treatment-emergent adverse events in the randomized study of an every-3-week schedule
 
PERCENTAGE OF PATIENTS
 
ABRAXANE 260 mg/m2 over 30 min (n=229)
ABRAXANE 260 mg/m2 over 30 min (n=229)
Paclitaxel injection 175 mg/m2 over 3 hb (n=225)
Paclitaxel injection 175 mg/m2 over 3 hb (n=225)
 
 
 
HEMATOLOGIC    
BONE MARROW    
Neutropenia    
<2.0 x 109/L 80 82
<0.5 x 109/L (Grade 4) 9 22
Thrombocytopenia    
<100 x 109/L 2 3
<50 x 109/L (Grade ≥3) <1 <1
Anemia    
<11 g/dL 33 25
<8 g/dL (Grade ≥3) 1 <1
Infections 24 20
Febrile Neutropenia 2 1
Neutropenic Sepsis <1 <1
Bleeding 2 2
NONHEMATOLOGIC    
HYPERSENSITIVITY REACTIONc    
All 4 12
Severed 0 2
CARDIOVASCULAR    
Vital Sign Changes During Administration    
Bradycardia <1 <1
Hypotension 5 5
Severe Cardiovascular Eventsd 3 4
ABNORMAL ECG    
All Patients 60 52
Patients With Normal Baseline 35 30
RESPIRATORY    
Cough 7 6
Dyspnea 12 9
SENSORY NEUROPATHY    
Any Symptoms 71 56
Severe Symptomsd 10 2
MYALGIA/ARTHRALGIA    
Any Symptoms 44 49
Severe Symptomsd 8 4
ASTHENIA    
Any Symptoms 47 39
Severe Symptomsd 8 3
FLUID RETENTION/EDEMA    
Any Symptoms 10 8
Severe Symptomsd 0 <1
GASTROINTESTINAL    
Nausea    
Any Symptoms 30 22
Severe Symptomsd 3 <1
Vomiting    
Any Symptoms 18 10
Severe Symptomsd 4 1
Diarrhea    
Any Symptoms 27 15
Severe Symptomsd <1 1
Mucositis    
Any Symptoms 7 6
Severe Symptomsd <1 0
ALOPECIA 90 94
HEPATIC (PATIENTS WITH NORMAL BASELINE)    
Bilirubin Elevations 7 7
Alkaline Phosphatase Elevations 36 31
AST (SGOT) Elevations 39 32
INJECTION SITE REACTION <1 1

AST=aspartate aminotransferase; ECG=electrocardiogram; SGOT=serum glutamic-oxaloacetic transaminase.

  • aBased on worst grade by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 2.
  • bPaclitaxel injection patients received premedication.
  • cIncludes treatment-related events related to hypersensitivity (eg, flushing, dyspnea, chest pain, hypotension) that began on a day of dosing.
  • dSevere events are defined as at least Grade 3 toxicity.

UNDERSTANDING DURATION AND DOSING

IN THE PHASE III MBC TRIAL

Patients treated with ABRAXANE received a median of 6 cycles of therapy

metastatic breast cancer dosing median cycle
  • The primary end point, recTLRR, was the evaluation of responses achieved in the first 6 cycles of therapy

FDA-Approved Dose and Schedule for ABRAXANE in Metastatic Breast Cancer:

  • Administer intravenously at a dose of 260 mg/m2
  • Administer over 30 minutes
  • Recommended schedule is once every 3 weeks
  • Premedication to prevent hypersensitivity reactions is generally not needed prior to the administration of ABRAXANE. Premedication may be needed in patients who have had prior hypersensitivity reactions to ABRAXANE. Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with this drug

FDA-Approved Dose and Schedule for ABRAXANE in Metastatic Breast Cancer:

  • Administer intravenously at a dose of 260 mg/m2
  • Administer over 30 minutes
  • Recommended schedule is once every 3 weeks
  • Premedication to prevent hypersensitivity reactions is generally not needed prior to the administration of ABRAXANE. Premedication may be needed in patients who have had prior hypersensitivity reactions to ABRAXANE. Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with this drug
  • Dose Modifications:
    Hepatic Impairment

    DOSE MODIFICATIONS

    FOR 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
    • 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
    • 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
    • Dosage recommendations are for the first course of therapy. The need for further dose adjustments in subsequent courses should be based on individual tolerance

     

    • Do not administer ABRAXANE to patients with total bilirubin >5 x ULN or AST >10 x ULN
    ULN=upper limit of normal.

    ABRAXANE dose

    metastatic breast cancer dosing bottle 260 metastatic breast cancer dosing bottle 200 metastatic breast cancer dosing bottle not recommended

    ILLUSTRATIVE
    PURPOSES ONLY

    • aA dose increase to 260 mg/m2 in subsequent courses should be considered if the patient tolerates the reduced dose for 2 cycles.
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  • Dose Modifications:
    Neuropathy

    DOSING FOR YOUR PATIENTS

    WHO EXPERIENCE SENSORY NEUROPATHY
    ABRAXANE dose-modification schedule for neuropathy

    Mild to Moderate

    The occurrence of Grade 1 or 2 sensory neuropathy does not generally require dose modification

    • In the phase III ABRAXANE MBC clinical trial, sensory neuropathy with any symptoms occurred in 71% of patients receiving ABRAXANE 260 mg/m2 over 30 minutes; sensory neuropathy with severe symptoms (defined as ≥ Grade 3 toxicity) occurred in 10% of patients receiving ABRAXANE

    Severe

    If ≥ Grade 3 sensory neuropathy develops, hold until resolution to Grade 1 or 2 followed by a dose reduction for all subsequent courses of ABRAXANE

    • In the phase III ABRAXANE MBC clinical trial, sensory neuropathy with any symptoms occurred in 71% of patients receiving ABRAXANE 260 mg/m2 over 30 minutes; sensory neuropathy with severe symptoms (defined as ≥ Grade 3 toxicity) occurred in 10% of patients receiving ABRAXANE

    Recurrent

    If severe (≥ Grade 3) neuropathy is recurrent, hold treatment until resolution to Grade 1 or 2, then reduce dose from 220 mg/m2 to 180 mg/m2 for all subsequent courses

    • In the phase III ABRAXANE MBC clinical trial, sensory neuropathy with any symptoms occurred in 71% of patients receiving ABRAXANE 260 mg/m2 over 30 minutes; sensory neuropathy with severe symptoms (defined as ≥ Grade 3 toxicity) occurred in 10% of patients receiving ABRAXANE

    ABRAXANE dose

    metastatic breast cancer dosing bottle hold or resume at 220 metastatic breast cancer dosing bottle 180

    ILLUSTRATIVE
    PURPOSES ONLY

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  • Dose Modifications:
    Neutropenia

    DOSING FOR YOUR PATIENTS

    WHO EXPERIENCE NEUTROPENIA
    ABRAXANE dose-modification schedule for neutropenia

    Mild to Moderate

    • If neutropenia is mild or moderate (Grade 1 or 2), no dose reduction is needed
    • ABRAXANE has a dose-reduction schedule for patients who experience severe neutropenia
    • Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to dosing on Day 1
    • In the phase III ABRAXANE MBC clinical trial, neutropenia (<2.0 x 109/L) occurred in 80% of patients receiving ABRAXANE 260 mg/m2 over 30 minutes; neutropenia (<0.5 x 109/L) occurred in 9% of patients receiving ABRAXANE

    Severe

    • If neutropenia is severe (neutrophils <500 cells/mm3 for 7 days or longer), reduce dose from 260 mg/m2 to 220 mg/m2 for subsequent courses
    • ABRAXANE has a dose-reduction schedule for patients who experience severe neutropenia
    • Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to dosing on Day 1
    • In the phase III ABRAXANE MBC clinical trial, neutropenia (<2.0 x 109/L) occurred in 80% of patients receiving ABRAXANE 260 mg/m2 over 30 minutes; neutropenia (<0.5 x 109/L) occurred in 9% of patients receiving ABRAXANE

    Recurrent

    • If severe neutropenia is recurrent, reduce dose from 220 mg/m2 to 180 mg/m2 for subsequent courses
    • ABRAXANE has a dose-reduction schedule for patients who experience severe neutropenia
    • Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to dosing on Day 1
    • In the phase III ABRAXANE MBC clinical trial, neutropenia (<2.0 x 109/L) occurred in 80% of patients receiving ABRAXANE 260 mg/m2 over 30 minutes; neutropenia (<0.5 x 109/L) occurred in 9% of patients receiving ABRAXANE

    ABRAXANE dose

    metastatic breast cancer dosing bottle 220 metastatic breast cancer dosing bottle 180

    ILLUSTRATIVE
    PURPOSES ONLY

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blue brushstroke mbc people metastatic breast cancer sparkler

WHEN RESPONSE RATES MATTER,

CHOOSE ABRAXANE FOR YOUR PATIENTS WITH MBC

CHOOSE ABRAXANE FOR YOUR PATIENTS WITH MBC

recTLRR IN THE ITT POPULATION

ABRAXANE

21.5%

(n=50/233)
(95% CI: 16.19%-26.73%)

VS

VS

Paclitaxel injection

11.1%

(n=25/227)
(95% CI: 6.94%-15.09%)

P=0.003a

recTLRR IN RELAPSED OR REFRACTORY PATIENTS

ABRAXANE

15.5%

(n=20/129)
(95% CI: 9.26%-21.75%)

VS

VS

Paclitaxel injection

8.4%

(n=12/143)
(95% CI: 3.85%-12.94%)

recTLRR IN RELAPSED OR REFRACTORY PATIENTS

ABRAXANE

15.5%

(n=20/129)
(95% CI: 9.26%-21.75%)

VS

Paclitaxel injection

8.4%

(n=12/143)
(95% CI: 3.85%-12.94%)

In the ITT population, there was no statistically significant difference in overall survival

(median OS 65.0 weeks vs 55.7 weeks, P=NS10)

Study design

Multicenter, 1:1 randomized, phase III study comparing ABRAXANE 260 mg/m2 IV q3w with paclitaxel injection 175 mg/m2 IV q3w in 460 patients with MBC. The primary efficacy end point was recTLRR. recTLRR was based on independent radiologic assessment of target lesions reconciled with investigator-reported responses for the first 6 cycles of therapy. The recTLRR was lower than the investigator-reported response rates, which are based on all cycles of therapy.

  • aFrom Cochran-Mantel-Haenszel test stratified by first-line vs > first-line therapy.