S:6.875”
`
`S:6.875”
`
`B:17.5”
`
`T:15.5”
`
`KADCYLA®: The first antibody-drug conjugate for
`HER2-positive metastatic breast cancer
`
`KADCYLA contains the active antibody
`trastuzumab, the cytotoxic agent DM1,
`and a stable linker
`
`Superior efficacy with a single agent 1
`
`Effective
`Jan 1, 2014
`
`J9354
`
`NEARLY 6-MONTH IMPROVEMENT IN MEDIAN OVERALL SURVIVAL (OS) 1
`100
` 30.9
`
`90
`
`80
`
`months
`
`HR=0.682
`95% CI: 0.548, 0.849
`P=0.0006
`
`70
`
`60
`
`50
`
`40
`
`30
`
`20
`
`10
`
`0
`
` 25.1
`
`months
`
`KADCYLA
`(n=495)
`No. of events: 149
`lapatinib + capecitabine
`(n=496)
`No. of events: 182
`
`Proportion surviving (%)
`
`B:11.5”
`
`T:10.5”
`
`S:9.875”
`
`0
`
`2
`
`4
`
`6
`
`8
`
`10
`
`12
`
`14
`
`No. at risk:
`KADCYLA
`lapatinib +
`capecitabine
`
`495
`496
`
`485
`471
`
`474
`453
`
`457
`435
`
`439
`403
`
`418
`368
`
`349
`297
`
`293
`240
`
`16
`18
`Months
`242
`197
`204
`159
`
`20
`
`22
`
`24
`
`164
`133
`
`136
`110
`
`111
`86
`
`26
`
`86
`63
`
`28
`
`62
`45
`
`30
`
`38
`27
`
`32
`
`28
`17
`
`34
`
`13
`7
`
`36
`
`5
`4
`
`Results of the randomized, open-label, Phase III EMILIA trial of KADCYLA (3.6 mg/kg IV, Day 1) vs the combination of lapatinib (1250 mg/day
`oral, once daily) and capecitabine (1000 mg/m2, oral, twice daily, Days 1-14) in 21-day cycles until disease progression in HER2+ MBC patients
`previously treated with trastuzumab and a taxane. Primary endpoints were OS, progression-free survival (PFS), and safety.1,2
`
`• 50% improvement in median PFS for KADCYLA vs lapatinib + capecitabine (9.6 months vs 6.4 months; HR=0.650;
`95% CI: 0.549, 0.771; P<0.0001)1
`• The most common NCI-CTCAE (version 3) adverse reactions Grades ≥3 (frequency >2%) were thrombocytopenia,
`increased transaminases, anemia, hypokalemia, peripheral neuropathy, and fatigue1
`
`Thrombocytopenia
`• In EMILIA, the incidence of ≥ Grade 3 thrombocytopenia was
`14.5% in the KADCYLA-treated group and 0.4% in the comparator
`group (overall incidence 31.2% and 3.3%, respectively)
`• Monitor platelet counts prior to initiation of KADCYLA and prior to
`each KADCYLA dose. Institute dose modifications as appropriate
`Neurotoxicity
`• In EMILIA, the incidence of ≥ Grade 3 peripheral neuropathy was
`2.2% in the KADCYLA-treated group and 0.2% in the comparator
`group (overall incidence 21.2% and 13.5%, respectively)
`• Monitor for signs or symptoms of neurotoxicity. KADCYLA should
`be temporarily discontinued in patients experiencing Grade 3 or 4
`peripheral neuropathy until resolution to ≤ Grade 2
`HER2 Testing
`• Detection of HER2 protein overexpression or gene amplification
`is necessary for selection of patients appropriate for KADCYLA.
`Perform using FDA approved tests by laboratories with
`demonstrated proficiency
`Extravasation
`• In KADCYLA clinical studies, reactions secondary to extravasation
`have been observed and were generally mild. The infusion site
`should be closely monitored for possible subcutaneous infiltration
`during drug administration. Specific treatment for KADCYLA
`extravasation is unknown
`
`Nursing Mothers
`• Discontinue nursing or discontinue KADCYLA taking into
`consideration the importance of the drug to the mother
`Adverse Reactions
`• The most common ADRs seen with KADCYLA in EMILIA
`(frequency > 25%) were nausea, fatigue, musculoskeletal pain,
`thrombocytopenia, increased transaminases, headache, and
`constipation. The most common NCI-CTCAE (version 3) ≥ Grade
`3 ADRs (frequency >2%) were thrombocytopenia, increased
`transaminases, anemia, hypokalemia, peripheral neuropathy
`and fatigue
`You are encouraged to report side effects to Genentech and the
`FDA. You may contact Genentech by calling 1-888-835-2555. You
`may contact the FDA by visiting www.fda.gov/medwatch or calling
`1-800-FDA-1088.
`Please see the following pages for brief summary of full
`Prescribing Information, including Boxed WARNINGS.
`For more information on KADCYLA, visit KADCYLA.com.
`
`References: 1. KADCYLA Prescribing Information. Genentech, Inc. May 2013. 2. Verma S, Miles D, Gianni L, et al;
`EMILIA Study Group. Trastuzumab emtansine for HER2-positive advanced breast cancer [published correction appears
`in N Engl J Med. 2013;368:2442]. N Engl J Med. 2012;367:1783-1791.
`
`Indication
`KADCYLA® (ado-trastuzumab emtansine), as a single agent, is indicated
`for the treatment of patients with HER2-positive (HER2+), metastatic
`breast cancer (MBC) who previously received trastuzumab and a taxane,
`separately or in combination. Patients should have either: received prior
`therapy for metastatic disease, or developed disease recurrence during
`or within six months of completing adjuvant therapy.
`Important Safety Information
`Boxed WARNINGS: HEPATOTOXICITY, CARDIAC TOXICITY,
`EMBRYO- FETAL TOXICITY
`• Do Not Substitute KADCYLA for or with Trastuzumab
`• Hepatotoxicity: Serious hepatotoxicity has been reported,
`including liver failure and death in patients treated with
`KADCYLA. Monitor serum transaminases and bilirubin prior to
`initiation of KADCYLA treatment and prior to each KADCYLA
`dose. Reduce dose or discontinue KADCYLA as appropriate in
`cases of increased serum transaminases or total bilirubin
`• Cardiac Toxicity: KADCYLA administration may lead to
`reductions in left ventricular ejection fraction (LVEF). Evaluate
`left ventricular function in all patients prior to and during
`treatment with KADCYLA. Withhold treatment for clinically
`significant decrease in left ventricular function
`• Embryo- Fetal Toxicity: Exposure to KADCYLA can result in
`embryo- fetal death or birth defects. Advise patients of these
`risks and the need for effective contraception
`
`© 2013 Genentech USA, Inc. All rights reserved. TDM0002133900 Printed in USA. (12/13)
`
`Additional Important Safety Information
`Left Ventricular Dysfunction (LVD)
`• Patients treated with KADCYLA are at increased risk of developing
`LVD. In EMILIA, LVD occurred in 1.8% of patients in the KADCYLA-
`treated group and in 3.3% in the comparator group. Permanently
`discontinue KADCYLA if LVEF has not improved or has declined further
`Pregnancy Registry
`• Advise patients to contact their healthcare provider immediately if
`they suspect they may be pregnant. Encourage women who may
`be exposed to KADCYLA during pregnancy to enroll in the MotHER
`Pregnancy Registry by contacting 1-800-690-6720
`Pulmonary Toxicity
`• Cases of interstitial lung disease (ILD), including pneumonitis, some
`leading to acute respiratory distress syndrome or fatal outcome have
`been reported in clinical trials with KADCYLA. In EMILIA, the overall
`frequency of pneumonitis was 1.2%
`• Treatment with KADCYLA should be permanently discontinued in
`patients diagnosed with ILD or pneumonitis
`Infusion-Related Reactions, Hypersensitivity Reactions
`• Treatment with KADCYLA has not been studied in patients who
`had trastuzumab permanently discontinued due to infusion-related
`reactions (IRR) and/or hypersensitivity reactions; treatment with
`KADCYLA is not recommended for these patients. In EMILIA, the
`overall frequency of IRRs in patients treated with KADCYLA was 1.4%
`• KADCYLA treatment should be interrupted in patients with severe
`IRR and permanently discontinued in the event of a life-threatening
`IRR. Patients should be closely monitored for IRR reactions, especially
`during the first infusion
`
`12/2/13 4:41 PM
`
`S&H
`
`GNH_FRN_Q37434C_JA_M04.indd 1
`
`IMMUNOGEN 2230, pg. 1
`Phigenic v. Immunogen
`IPR2014-00676
`
`
`
`S:6.875”
`
`B:17.5”
`
`T:15.5”
`
`KADCYLA®: The first antibody-drug conjugate for
`HER2-positive metastatic breast cancer
`
`KADCYLA contains the active antibody
`trastuzumab, the cytotoxic agent DM1,
`and a stable linker
`
`Superior efficacy with a single agent 1
`
`Effective
`Jan 1, 2014
`
`J9354
`
`NEARLY 6-MONTH IMPROVEMENT IN MEDIAN OVERALL SURVIVAL (OS) 1
`100
` 30.9
`
`90
`
`80
`
`months
`
`HR=0.682
`95% CI: 0.548, 0.849
`P=0.0006
`
`70
`
`60
`
`50
`
`40
`
`30
`
`20
`
`10
`
`0
`
` 25.1
`
`months
`
`KADCYLA
`(n=495)
`No. of events: 149
`lapatinib + capecitabine
`(n=496)
`No. of events: 182
`
`Proportion surviving (%)
`
`B:11.5”
`
`T:10.5”
`
`S:9.875”
`
`0
`
`2
`
`4
`
`6
`
`8
`
`10
`
`12
`
`14
`
`No. at risk:
`KADCYLA
`lapatinib +
`capecitabine
`
`495
`496
`
`485
`471
`
`474
`453
`
`457
`435
`
`439
`403
`
`418
`368
`
`349
`297
`
`293
`240
`
`16
`18
`Months
`242
`197
`204
`159
`
`20
`
`22
`
`24
`
`164
`133
`
`136
`110
`
`111
`86
`
`26
`
`86
`63
`
`28
`
`62
`45
`
`30
`
`38
`27
`
`32
`
`28
`17
`
`34
`
`13
`7
`
`36
`
`5
`4
`
`Results of the randomized, open-label, Phase III EMILIA trial of KADCYLA (3.6 mg/kg IV, Day 1) vs the combination of lapatinib (1250 mg/day
`oral, once daily) and capecitabine (1000 mg/m2, oral, twice daily, Days 1-14) in 21-day cycles until disease progression in HER2+ MBC patients
`previously treated with trastuzumab and a taxane. Primary endpoints were OS, progression-free survival (PFS), and safety.1,2
`
`• 50% improvement in median PFS for KADCYLA vs lapatinib + capecitabine (9.6 months vs 6.4 months; HR=0.650;
`95% CI: 0.549, 0.771; P<0.0001)1
`• The most common NCI-CTCAE (version 3) adverse reactions Grades ≥3 (frequency >2%) were thrombocytopenia,
`increased transaminases, anemia, hypokalemia, peripheral neuropathy, and fatigue1
`
`Thrombocytopenia
`• In EMILIA, the incidence of ≥ Grade 3 thrombocytopenia was
`14.5% in the KADCYLA-treated group and 0.4% in the comparator
`group (overall incidence 31.2% and 3.3%, respectively)
`• Monitor platelet counts prior to initiation of KADCYLA and prior to
`each KADCYLA dose. Institute dose modifications as appropriate
`Neurotoxicity
`• In EMILIA, the incidence of ≥ Grade 3 peripheral neuropathy was
`2.2% in the KADCYLA-treated group and 0.2% in the comparator
`group (overall incidence 21.2% and 13.5%, respectively)
`• Monitor for signs or symptoms of neurotoxicity. KADCYLA should
`be temporarily discontinued in patients experiencing Grade 3 or 4
`peripheral neuropathy until resolution to ≤ Grade 2
`HER2 Testing
`• Detection of HER2 protein overexpression or gene amplification
`is necessary for selection of patients appropriate for KADCYLA.
`Perform using FDA approved tests by laboratories with
`demonstrated proficiency
`Extravasation
`• In KADCYLA clinical studies, reactions secondary to extravasation
`have been observed and were generally mild. The infusion site
`should be closely monitored for possible subcutaneous infiltration
`during drug administration. Specific treatment for KADCYLA
`extravasation is unknown
`
`Nursing Mothers
`• Discontinue nursing or discontinue KADCYLA taking into
`consideration the importance of the drug to the mother
`Adverse Reactions
`• The most common ADRs seen with KADCYLA in EMILIA
`(frequency > 25%) were nausea, fatigue, musculoskeletal pain,
`thrombocytopenia, increased transaminases, headache, and
`constipation. The most common NCI-CTCAE (version 3) ≥ Grade
`3 ADRs (frequency >2%) were thrombocytopenia, increased
`transaminases, anemia, hypokalemia, peripheral neuropathy
`and fatigue
`You are encouraged to report side effects to Genentech and the
`FDA. You may contact Genentech by calling 1-888-835-2555. You
`may contact the FDA by visiting www.fda.gov/medwatch or calling
`1-800-FDA-1088.
`Please see the following pages for brief summary of full
`Prescribing Information, including Boxed WARNINGS.
`For more information on KADCYLA, visit KADCYLA.com.
`
`References: 1. KADCYLA Prescribing Information. Genentech, Inc. May 2013. 2. Verma S, Miles D, Gianni L, et al;
`EMILIA Study Group. Trastuzumab emtansine for HER2-positive advanced breast cancer [published correction appears
`in N Engl J Med. 2013;368:2442]. N Engl J Med. 2012;367:1783-1791.
`
`Indication
`KADCYLA® (ado-trastuzumab emtansine), as a single agent, is indicated
`for the treatment of patients with HER2-positive (HER2+), metastatic
`breast cancer (MBC) who previously received trastuzumab and a taxane,
`separately or in combination. Patients should have either: received prior
`therapy for metastatic disease, or developed disease recurrence during
`or within six months of completing adjuvant therapy.
`Important Safety Information
`Boxed WARNINGS: HEPATOTOXICITY, CARDIAC TOXICITY,
`EMBRYO- FETAL TOXICITY
`• Do Not Substitute KADCYLA for or with Trastuzumab
`• Hepatotoxicity: Serious hepatotoxicity has been reported,
`including liver failure and death in patients treated with
`KADCYLA. Monitor serum transaminases and bilirubin prior to
`initiation of KADCYLA treatment and prior to each KADCYLA
`dose. Reduce dose or discontinue KADCYLA as appropriate in
`cases of increased serum transaminases or total bilirubin
`• Cardiac Toxicity: KADCYLA administration may lead to
`reductions in left ventricular ejection fraction (LVEF). Evaluate
`left ventricular function in all patients prior to and during
`treatment with KADCYLA. Withhold treatment for clinically
`significant decrease in left ventricular function
`• Embryo- Fetal Toxicity: Exposure to KADCYLA can result in
`embryo- fetal death or birth defects. Advise patients of these
`risks and the need for effective contraception
`
`© 2013 Genentech USA, Inc. All rights reserved. TDM0002133900 Printed in USA. (12/13)
`
`Additional Important Safety Information
`Left Ventricular Dysfunction (LVD)
`• Patients treated with KADCYLA are at increased risk of developing
`LVD. In EMILIA, LVD occurred in 1.8% of patients in the KADCYLA-
`treated group and in 3.3% in the comparator group. Permanently
`discontinue KADCYLA if LVEF has not improved or has declined further
`Pregnancy Registry
`• Advise patients to contact their healthcare provider immediately if
`they suspect they may be pregnant. Encourage women who may
`be exposed to KADCYLA during pregnancy to enroll in the MotHER
`Pregnancy Registry by contacting 1-800-690-6720
`Pulmonary Toxicity
`• Cases of interstitial lung disease (ILD), including pneumonitis, some
`leading to acute respiratory distress syndrome or fatal outcome have
`been reported in clinical trials with KADCYLA. In EMILIA, the overall
`frequency of pneumonitis was 1.2%
`• Treatment with KADCYLA should be permanently discontinued in
`patients diagnosed with ILD or pneumonitis
`Infusion-Related Reactions, Hypersensitivity Reactions
`• Treatment with KADCYLA has not been studied in patients who
`had trastuzumab permanently discontinued due to infusion-related
`reactions (IRR) and/or hypersensitivity reactions; treatment with
`KADCYLA is not recommended for these patients. In EMILIA, the
`overall frequency of IRRs in patients treated with KADCYLA was 1.4%
`• KADCYLA treatment should be interrupted in patients with severe
`IRR and permanently discontinued in the event of a life-threatening
`IRR. Patients should be closely monitored for IRR reactions, especially
`during the first infusion
`
`12/2/13 4:41 PM
`
`S&H
`
`GNH_FRN_Q37434C_JA_M04.indd 1
`
`IMMUNOGEN 2230, pg. 1
`Phigenic v. Immunogen
`IPR2014-00676
`
`
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