test@unify.com
`To: kamila.alberti-correa@meltmedia.com
`Proven survival benefit for your HER2+ MBC patients
`
`
`
`Dear [Healthcare Provider Name]:
`
`November 11, 2013 11:14 AM
`
`[Customize the text in this paragraph with your own message to the Healthcare Provider. Based on
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`[Signature]
`KADCYLA demonstrated clinical benefits in patients
`with HER2+ MBC
`
`Proven survival
`benefit1
`
`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
`
`KADCYLA is the first HER2-targeted antibody-drug conjugate for
`HER2+ metastatic breast cancer.
`In the Phase III EMILIA trial of KADCYLA vs the combination of
`lapatinib + capecitabine, KADCYLA extended median overall survival
`(OS) and significantly improved median progression-free survival (PFS).
`KADCYLA extended median OS by nearly 6 months1
`PRIMARY ENDPOINT: OVERALL SURVIVAL (OS)
`
`IMMUNOGEN 2235, pg. 1
`Phigenic v. Immunogen
`IPR2014-00676
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`

`
`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 by independent review1
`• 9.6 months median PFS with KADCYLA vs 6.4 months with lapatinib + capecitabine;
`P<0.0001
`
`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
`
`For more information about these and other
`EMILIA trial endpoints, visit KADCYLA.com.
`
`Important Safety Information
`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
`
`IMMUNOGEN 2235, pg. 2
`Phigenic v. Immunogen
`IPR2014-00676
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`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 download the full Prescribing Information for additional important safety
`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 and Supplementary Appendix.
`
`TDM0002192700 (11/13)
`
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`
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