Patients and Caregivers

Helpful Resources for Your Practice

KADCYLA Access Solutions offers a range of access and reimbursement resources for your patients and practice after KADCYLA is prescribed, including help with benefits investigations (BIs), resources for prior authorizations (PAs), sample billing and coding information, resources for denials and appeals, information about distribution and referrals to potential financial assistance options.

Quick Links

Help with coverage (BIs and PAs)
Reimbursement (billing, coding and appeals)
Online patient enrollment
KADCYLA Distribution
Product issues

Coverage

Get help understanding insurance benefits and coverage, such as with benefits investigations and prior authorization resources.

Benefits investigations

KADCYLA Access Solutions can conduct a benefits investigation (BI) which can determine:

  • If treatment is covered
  • If treatment is denied
  • If a prior authorization or pre-determination is required*
  • If your patient's insurance plan has a mandated or preferred SP

*If your patient’s request for a prior authorization is not granted, your KADCYLA Access Solutions Specialist can work with you to determine your next steps.

Option 1: Submit forms online

If your practice has a registered account for My Patient Solutions, you can get started by logging into your account.

Don't have an account?

Your patient is required to complete the Patient Consent Form. You can either upload their Patient Consent Form as part of your application or have your patient submit the form via fax, text or e-submit.

  • An online tool to help you enroll patients in KADCYLA Access Solutions and manage your service requests at your convenience.

Option 2: Print forms and fax or text

Step 1: Print one of the Patient Consent Forms below for your patient to complete.

Step 2: Print and complete the Prescriber Service Form below.

Step 3: Submit the completed forms via fax or text.

Both forms are required. We must have both the Patient Consent Form and the Prescriber Service Form before we can help you.

What to expect next:

  • The request will be processed within five business days upon receipt of both required forms.
  • Your office will be contacted to discuss the application outcome and any next steps.

Genentech reserves the right to modify or discontinue the program at any time and to verify the accuracy of information submitted.

The completion and submission of coverage- or reimbursement-related documentation are the responsibility of the patient and healthcare provider. Genentech makes no representation or guarantee concerning coverage or reimbursement for any service or item.

Reimbursement

Sample coding information and resources for denials and appeals

KADCYLA Sample Coding

This coding information may assist you as you complete the payer forms for KADCYLA. These tables are provided for informational purposes only. Please visit CMS.gov or other payers’ websites to obtain additional guidance on their processes related to billing and coding.

Download sample coding and the Important Safety Information for KADCYLA below.

Sample Coding and Safety Information for KADCYLA

Correct coding is the responsibility of the provider submitting the claim for the item or service. Please check with the payer to verify codes and special billing requirements. Genentech does not make any representation or guarantee concerning reimbursement or coverage for any service or item.

Appeals

If your patient’s health insurance plan has issued a denial, your KADCYLA Access Solutions Specialist can provide resources as you prepare an appeal submission, as per your patient’s plan requirements. 

If a plan issues a denial: 

  1. The denial should be reviewed, along with the health insurance plan’s guidelines to determine what to include in your patient’s appeal submission.
  2. Your KADCYLA Access Solutions Specialist has local payer coverage expertise and can help you determine specific requirements for your patient.

A sample appeal letter and additional considerations are available on the Practice Forms and Documents page.

Appeals cannot be completed or submitted by Genentech on your behalf.

Online patient enrollment

Submit KADCYLA Access Solutions forms and check the status of your service requests online using My Patient Solutions

My Patient Solutions is an online tool to help you enroll patients in KADCYLA Access Solutions and manage your service requests, all through one portal. It allows you the flexibility to work with KADCYLA Access Solutions when it’s convenient for you.

With My Patient Solutions, you can:

  • Enroll and re-enroll patients in financial assistance programs entirely online
  • Communicate with your KADCYLA Access Solutions Specialist
  • Easily identify next steps for service requests
  • View Benefits Investigation reports for all your enrolled patients
  • Follow up on prior authorizations or appeals
  • View co-pay assistance outcomes and referral information

How to register

Account registration can be completed by one person for the entire practice and for multiple practice locations. For help with registration or if you have questions, call us at 877-GENENTECH (877-436-3683) (6AM-5PM PST, Monday through Friday).

Register for My Patient Solutions

KADCYLA Distribution

Genentech has contracted with a network of authorized specialty distributors and specialty pharmacies (SPs) to service practices choosing to prescribe KADCYLA. 

These partners have made a commitment to product integrity and have agreed to distribute only products purchased directly from Genentech and not to distribute KADCYLA through secondary channels.

Authorized Distributors and Specialty Pharmacies

For a full list of authorized distributors and in-network specialty pharmacies, please visit the Genentech Access Solutions website or contact KADCYLA Access Solutions at 888-249-4918.

About Buy and Bill

With Buy and Bill, the practice purchases the medication in advance, then bills the patient's health insurance plan for reimbursement. The practice is responsible for storing and handling the drug as well as collecting the patient's co-pay for both the drug and its administration. With Buy and Bill, practices can maintain a stock of the drug, giving them the flexibility to treat patients when clinically appropriate.

About Specialty Pharmacies

KADCYLA Access Solutions works with specialty pharmacies (SPs) to help patients receive their prescribed Genentech medicines.

In addition to distributing medicines, an SP may provide the following services:

  • Reimbursement resources
  • Clinical services to support patients throughout their treatment
  • The ability to manage the specialty handling and shipping needs linked with many specialty therapies

You can work with your preferred SP or contact KADCYLA Access Solutions to learn which SP the patient’s health insurance plan mandates or prefers.

Genentech does not influence or advocate the use of any one specialty distributor or specialty pharmacy. We make no representation or guarantee of service or coverage of any item. For any product-specific distribution questions, call KADCYLA Access Solutions at 888-249-4918 (6AM-5PM PST, Monday through Friday).

Product issues

We are serious about patient safety. If your Genentech product is spoiled, expired or damaged, we may be able to help you replace it.

Need more help? Click here to find the latest information.

Please contact Genentech Customer Service at (800) 551-2231 for any order or return-related questions.

Contact Us

Questions? Contact KADCYLA Access Solutions

Call 888-249-4918 (Mon.–Fri., 6AM–5PM PST)

NEXT: Practice Forms & Documents
Financial support

Financial Support

Find the right financial resources option for your patients.

Explore Options

    • Gianni L, et al. Lancet Oncol. 2016;17(6):791-800.

      Gianni L, et al. Lancet Oncol. 2016;17(6):791-800.

    • Data on file. Genentech, Inc.

      Data on file. Genentech, Inc.

    • Cortazar P, et al. Lancet. 2014;384(9938):164-172.

      Cortazar P, et al. Lancet. 2014;384(9938):164-172.

    • KADCYLA Prescribing Information. Genentech, Inc. 2022.

      KADCYLA Prescribing Information. Genentech, Inc. 2022.

    • Roche.com. FDA approves Roche's Kadcyla (trastuzumab emtansine), the first antibody-drug conjugate for treating HER2-positive metastatic breast cancer.

      Roche.com. FDA approves Roche's Kadcyla (trastuzumab emtansine), the first antibody-drug conjugate for treating HER2-positive metastatic breast cancer.

    • 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.

      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.

    • Junttila TT, Li G, Parsons K, Phillips GL, Sliwkowski MX. Trastuzumab-DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer. Breast Cancer Res Treat. 2011;128:347-356.

      Junttila TT, Li G, Parsons K, Phillips GL, Sliwkowski MX. Trastuzumab-DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer. Breast Cancer Res Treat. 2011;128:347-356.

    • Staudecher AH, Brown MP. Antibody drug conjugates and bystander killing: is antigen-dependent internalisation required? Br J Cancer. 2017;117(12):1736-1742.

      Staudecher AH, Brown MP. Antibody drug conjugates and bystander killing: is antigen-dependent internalisation required? Br J Cancer. 2017;117(12):1736-1742.

    • Lewis Phillips GD, Li G, Dugger DL, et al. Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Res. 2008;68(22):9280-9290.

      Lewis Phillips GD, Li G, Dugger DL, et al. Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Res. 2008;68(22):9280-9290.

    • Nahta R, Esteva FJ. Herceptin: mechanisms of action and resistance. Cancer Lett. 2006; 232:123-138.

      Nahta R, Esteva FJ. Herceptin: mechanisms of action and resistance. Cancer Lett. 2006; 232:123-138.

    • von Minckwitz G, Huang CS, Mano MS, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med. 2019;380(7):617-628.

      von Minckwitz G, Huang CS, Mano MS, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med. 2019;380(7):617-628.

    • Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V2.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed March 28, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN 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.

      Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V2.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed March 28, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN 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.

    • Denduluri N, Somerfield MR, Chavez-MacGregor M, et al. Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer: ASCO Guideline Update. J Clin Oncol. 2021;39(6):685-693.

      Denduluri N, Somerfield MR, Chavez-MacGregor M, et al. Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer: ASCO Guideline Update. J Clin Oncol. 2021;39(6):685-693.

    • Loibl S, Mano MS, Untch M, et al. Phase III study of adjuvant ado-trastuzumab emtansine vs trastuzumab for residual invasive HER2-positive early breast cancer after neoadjuvant chemotherapy and HER2-targeted therapy: KATHERINE final IDFS and updated OS analysis. Presented at: San Antonio Breast Cancer Symposium; December 5-9, 2023; San Antonio, TX. Accessed January 29, 2024.

      Loibl S, Mano MS, Untch M, et al. Phase III study of adjuvant ado-trastuzumab emtansine vs trastuzumab for residual invasive HER2-positive early breast cancer after neoadjuvant chemotherapy and HER2-targeted therapy: KATHERINE final IDFS and updated OS analysis. Presented at: San Antonio Breast Cancer Symposium; December 5-9, 2023; San Antonio, TX. Accessed January 29, 2024.

    • Geyer CE, et al. Phase III study of trastuzumab emtansine (T-DM1) vs trastuzumab as adjuvant therapy in patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy including trastuzumab: primary results from KATHERINE (NSABP B-50-I, GBG 77 and Roche BO27938). Presented at: San Antonio Breast Cancer Symposium; December 4-8, 2018.

      Geyer CE, et al. Phase III study of trastuzumab emtansine (T-DM1) vs trastuzumab as adjuvant therapy in patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy including trastuzumab: primary results from KATHERINE (NSABP B-50-I, GBG 77 and Roche BO27938). Presented at: San Antonio Breast Cancer Symposium; December 4-8, 2018.

    Indications/Important Safety Information

    Indications

    Early Breast Cancer (EBC)

    KADCYLA, as a single agent, is indicated for the adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment.

    Select patients for therapy based on an FDA-approved companion diagnostic for KADCYLA.

    Metastatic Breast Cancer (MBC)

    KADCYLA, as a single agent, is indicated for the treatment of patients with HER2-positive, metastatic breast cancer 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.

    Select patients for therapy based on an FDA-approved companion diagnostic for KADCYLA.

    Important Safety Information

    BOXED WARNINGS: HEPATOTOXICITY, CARDIAC TOXICITY, EMBRYO-FETAL TOXICITY

    • 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 during pregnancy can result in embryo-fetal harm. Advise patients of these risks and the need for effective contraception

    Warnings and Precautions

    Hepatotoxicity

    Hepatotoxicity, predominantly in the form of asymptomatic increases in the concentrations of serum transaminases, has been observed in clinical trials with KADCYLA. Serious hepatotoxicity, including 3 fatal cases, has been observed in clinical trials (n=1624) with KADCYLA as single-agent. The two fatal cases of severe drug-induced liver injury and associated hepatic encephalopathy occurred in MBC clinical trials with KADCYLA. Some of the patients experiencing hepatotoxicity had comorbidities and/or concomitant medications with known hepatotoxic potential.

    Monitor serum transaminases and bilirubin prior to initiation of KADCYLA treatment and prior to each KADCYLA dose. Patients with known active liver disease (such as hepatitis B virus or hepatitis C virus) were excluded from EMILIA (for patients with metastatic breast cancer [MBC]) and KATHERINE (for patients with early breast cancer [EBC]) studies. Reduce dose or discontinue KADCYLA as appropriate in cases of increased serum transaminases and/or total bilirubin. Permanently discontinue KADCYLA treatment in patients with serum transaminases >3 × ULN and concomitant total bilirubin >2 × ULN.

    In clinical trials of KADCYLA, cases of nodular regenerative hyperplasia (NRH) of the liver have been identified from liver biopsies (5 cases out of 1624, 1 of which was fatal). Two of these five cases of NRH were observed in EMILIA and two were observed in KATHERINE. Diagnosis can be confirmed only by histopathology. NRH should be considered in all patients with clinical symptoms of portal hypertension and/or cirrhosis-like pattern seen on the computed tomography scan of the liver but with normal transaminases and no manifestations of cirrhosis. Upon NRH diagnosis, KADCYLA treatment must be permanently discontinued.

    Left Ventricular Dysfunction

    Patients treated with KADCYLA are at increased risk of developing left ventricular dysfunction. A decrease of LVEF to <40% has been observed in patients treated with KADCYLA. Serious cases of heart failure, with no fatal cases, have been observed in clinical trials with KADCYLA.

    In EMILIA, left ventricular dysfunction occurred in 1.8% of patients in the KADCYLA group and 3.3% of patients in the lapatinib + capecitabine group. In KATHERINE, left ventricular dysfunction occurred in 0.4% of patients in the KADCYLA group and 0.6% of patients in the trastuzumab group.

    Based on limited data from a retrospective observational study, 22% (7 of 32) of patients with HER2-positive MBC with a baseline LVEF of 40-49% treated with KADCYLA developed congestive heart failure (CHF) or a >10% reduction in LVEF.

    Assess LVEF prior to initiation of KADCYLA and at regular intervals (e.g. every 3 months) during treatment to ensure the LVEF is within the institution’s normal limits. KADCYLA has not been studied in an adequately controlled study in patients with LVEF <50%.

    For patients with MBC, if at routine monitoring LVEF is <40%, or is 40% to 45% with a ≥10% absolute decrease below the pretreatment value, withhold KADCYLA and repeat LVEF assessment within approximately 3 weeks. Permanently discontinue KADCYLA if the LVEF has not improved or has declined further.

    For patients with EBC, if at routine monitoring LVEF is <45%, or is 45% to 49% with a ≥10% absolute decrease below the pretreatment value, withhold KADCYLA and repeat LVEF assessment within approximately 3 weeks. Permanently discontinue KADCYLA if the LVEF has not improved or has declined further.

    Embryo-Fetal Toxicity

    KADCYLA can cause fetal harm when administered to a pregnant woman. Cases of oligohydramnios, and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities and neonatal death were observed in the post-marketing setting in patients treated with trastuzumab, the antibody component of KADCYLA. DM1, the cytotoxic component of KADCYLA, can cause embryo-fetal toxicity, based on its mechanism of action.

    Verify the pregnancy status of females of reproductive potential prior to the initiation of KADCYLA. Advise pregnant women and females of reproductive potential that exposure to KADCYLA during pregnancy or within 7 months prior to conception can result in fetal harm. Advise females of reproductive potential to use effective contraception during treatment and for 7 months following the last dose of KADCYLA. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with KADCYLA and for 4 months following the last dose.

    If KADCYLA is administered during pregnancy, or if a patient becomes pregnant while receiving KADCYLA or within 7 months of the last dose of KADCYLA, immediately report exposure to Genentech at 1-888-835-2555.

    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. Signs and symptoms include dyspnea, cough, fatigue, and pulmonary infiltrates.

    In patients with MBC, pneumonitis was reported at an incidence of 0.8% (7 out of 884 treated patients), with one case of Grade 3 pneumonitis. The overall incidence of pneumonitis was 1.2% in EMILIA.

    In KATHERINE, pneumonitis was reported at an incidence of 1.1% (8 out of 740 patients treated with KADCYLA), with one case of Grade 3 pneumonitis. Radiation pneumonitis was reported at an incidence of 1.8% (11 out of 623 patients treated with adjuvant radiotherapy and KADCYLA), with 2 cases of Grade 3 radiation pneumonitis.

    Permanently discontinue treatment with KADCYLA in patients diagnosed with ILD or pneumonitis. For patients with radiation pneumonitis in the adjuvant setting, KADCYLA should be permanently discontinued for Grade ≥ 3 or for Grade 2 not responding to standard treatment.

    Patients with dyspnea at rest due to complications of advanced malignancy and comorbidities and receiving concurrent pulmonary radiation therapy may be at increased risk of pulmonary toxicity.

    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; treatment with KADCYLA is not recommended for these patients.

    Infusion-related reactions, characterized by one or more of the following symptoms—flushing, chills, pyrexia, dyspnea, hypotension, wheezing, bronchospasm, and tachycardia—have been reported in clinical trials of KADCYLA. In EMILIA, the overall incidence of IRR in patients treated with KADCYLA was 1.4%. In KATHERINE, the overall incidence of IRR in patients treated with KADCYLA was 1.6%. In most patients, these reactions resolved over the course of several hours to a day after the infusion was terminated.

    KADCYLA treatment should be interrupted in patients with severe IRR and permanently discontinued in the event of a life-threatening IRR. Patients should be observed closely for IRR, especially during the first infusion.

    One case of a serious, allergic/anaphylactic-like reaction has been observed in clinical trials of single-agent KADCYLA. Medications to treat such reactions, as well as emergency equipment, should be available for immediate use.

    Hemorrhage

    Cases of hemorrhagic events, including central nervous system, respiratory, and gastrointestinal hemorrhage, have been reported in clinical trials with KADCYLA. Some of these bleeding events resulted in fatal outcomes. In EMILIA, the overall incidence of hemorrhage was 32% in the KADCYLA group and 16% in the lapatinib + capecitabine group. The incidence of Grade ≥ 3 hemorrhage was 1.8% in the KADCYLA group and 0.8% in the lapatinib + capecitabine group. In KATHERINE, the overall incidence of hemorrhage was 29% in the KADCYLA group and 10% in the trastuzumab group. The incidence of Grade ≥ 3 hemorrhage was 0.4% in the KADCYLA group, with one fatal case of intracranial hemorrhage, and 0.3% in the trastuzumab group.

    Although in some of the observed cases, the patients were also receiving anticoagulation therapy or antiplatelet therapy, or had thrombocytopenia; in others, there were no known additional risk factors. Use caution with these agents and consider additional monitoring when concomitant use is medically necessary.

    Thrombocytopenia

    Thrombocytopenia was reported in clinical trials of KADCYLA. The majority of these patients had Grade 1 or 2 events (< LLN to ≥50,000/mm3) with the nadir occurring by day 8 and generally improving to Grade 0 or 1 (≥75,000/mm3) by the next scheduled dose. In clinical trials of KADCYLA, the incidence and severity of thrombocytopenia were higher in Asian patients.

    In EMILIA, the overall incidence of thrombocytopenia was 31% in the KADCYLA group and 3.3% in the lapatinib + capecitabine group. The incidence of Grade ≥ 3 thrombocytopenia was 15% in the KADCYLA group and 0.4% in the lapatinib + capecitabine group. In Asian patients, the incidence of Grade ≥ 3 thrombocytopenia was 45% and 1.3%, respectively.

    In KATHERINE, the overall incidence of thrombocytopenia was 29% in the KADCYLA group and 2.4% in the trastuzumab group. The incidence of Grade ≥ 3 thrombocytopenia was 6% in the KADCYLA group and 0.3% in the trastuzumab group. In Asian patients, the incidence of Grade ≥ 3 thrombocytopenia was 19% and 0%, respectively. The overall incidence of thrombocytopenia in the KADCYLA group for Asian patients was 50%.

    Monitor platelet counts prior to initiation of KADCYLA and prior to each KADCYLA dose. KADCYLA has not been studied in patients with platelet counts <100,000/mm3 prior to initiation of treatment. In the event of decreased platelet count to Grade ≥ 3 (<50,000/mm3), do not administer KADCYLA until platelet counts recover to Grade 1 (≥75,000/mm3). Closely monitor patients with thrombocytopenia (< 100,000/mm3) and patients on anti-coagulant treatment during treatment with KADCYLA.

    Neurotoxicity

    Peripheral neuropathy, mainly as Grade 1 and predominantly sensory, was reported in clinical trials of KADCYLA. In EMILIA, the overall incidence of peripheral neuropathy was 21% in the KADCYLA group and 14% in the lapatinib + capecitabine group. The incidence of Grade ≥ 3 peripheral neuropathy was 2.2% and 0.2%, respectively.

    In KATHERINE, the overall incidence of peripheral neuropathy was 32% in the KADCYLA group and 17% in the trastuzumab group. Peripheral neuropathy, including sensory and motor peripheral neuropathy, was not resolved in 30% of cases for KADCYLA treated patients at the time of the primary IDFS analysis for KATHERINE. The incidence of Grade ≥ 3 peripheral neuropathy was 1.6% in the KADCYLA group and 0.1% in the trastuzumab group.

    KADCYLA should be temporarily discontinued in patients experiencing Grade 3 or 4 peripheral neuropathy until resolution to Grade ≤ 2. Monitor patients on an ongoing basis for signs/symptoms of neurotoxicity.

    Extravasation

    In KADCYLA clinical studies, reactions secondary to extravasation have been observed. These reactions, observed more frequently within 24 hours of infusion, were usually mild and comprised erythema, tenderness, skin irritation, pain, or swelling at the infusion site. Specific treatment for KADCYLA extravasation is unknown. Closely monitor the infusion site for possible subcutaneous infiltration during drug administration.

    Adverse Reactions

    Early Breast Cancer

    The most common adverse reactions seen with KADCYLA in the KATHERINE trial (frequency >25%) were fatigue, nausea, increased transaminases, musculoskeletal pain, hemorrhage, thrombocytopenia, headache, peripheral neuropathy, and arthralgia. The most common NCI–CTCAE (version 3) Grade ≥ 3 adverse reactions (frequency >2%) were thrombocytopenia and hypertension.

    Metastatic Breast Cancer

    The most common adverse reactions (≥25%) with KADCYLA were fatigue, nausea, musculoskeletal pain, hemorrhage, thrombocytopenia, headache, increased transaminases, constipation and epistaxis. In EMILIA, the most common NCI–CTCAE (version 3) Grade ≥ 3 adverse reactions (frequency >2%) were thrombocytopenia, increased transaminases, anemia, hypokalemia, peripheral neuropathy, and fatigue.

    Use in Specific Populations

    Lactation

    There is no information regarding the presence of ado-trastuzumab emtansine in human milk, the effects on the breastfed infant, or the effects on milk production. DM1, the cytotoxic component of KADCYLA, may cause serious adverse reactions in breastfed infants based on its mechanism of action. Advise women not to breastfeed during treatment and for 7 months following the last dose of KADCYLA.

    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 full Prescribing Information for additional Important Safety Information, including BOXED WARNINGS.

    • This image shows the components of KADCYLA:

      Trastuzumab–monoclonal antibody4

      • Selectively binds to HER2

      MCC–stable linker4,6

      • Stabilizes KADCYLA in circulation to release DM1 after entering the target cell

      DM1–cytotoxic agent4,7

      • Approximately 20 to 200 times more potent than taxanes and vinca alkaloids
      • Provides cytotoxicity previously unavailable for clinical use

    • Overview
      This image shows the trial design of KATHERINE.

      Data
      KATHERINE was a randomized, multicenter, open-label trial of 1,486 patients with HER2+ early breast cancer. Patients were required to have had residual invasive disease in the breast and/or axillary lymph nodes following neoadjuvant treatment with taxane + trastuzumab-based therapy. Patients were randomized to 3.6 mg/kg of KADCYLA or 6 mg/kg of Herceptin® (trastuzumab), with 743 patients in each arm.

    • Overview
      This image shows a Kaplan-Meier curve of invasive disease-free survival (iDFS) in KATHERINE.

      Data
      Invasive disease-free survival, the primary end point, was significantly higher among patients who received KADCYLA than among those who received trastuzumab (hazard ratio, 0.54, 95% confidence interval [CI], 0.44-0.66; P<0.0001). 7-year iDFS was 80.8% in the KADCYLA group, compared to 67.1% in the trastuzumab group, representing a 46% reduction in the risk of recurrence

    • Overview
      This image shows where KADCYLA fits in the HER2+ early breast cancer treatment plan and how many cycles of it to give.

      Details
      Following 3-6 cycles of neoadjuvant taxane + trastuzumab-based treatment, and surgery, give KADCYLA for 14 cycles, or until disease recurrence or unmanageable toxicity occurs.

    • Overview
      This image shows the infusion schedule for KADCYLA in early breast cancer.

      Details
      The initial infusion of KADCYLA in EBC takes 90 minutes plus an observation time of at least 90 minutes to monitor for infusion-related reactions. If prior infusions were well tolerated, subsequent infusions take 30 minutes plus an observation time of at least 30 minutes.

      Treat for a total of 14 cycles (every 3 weeks) unless there is disease recurrence or unmanageable toxicity.

    • Overview
      This image shows the dose reduction schedule for adverse reactions to KADCYLA.

      Details
      The starting dose for KADCYLA is 3.6 mg/kg. The first dose reduction for KADCYLA is 3 mg/kg. The second dose reduction for KADCYLA is 2.4 mg/kg. After that, discontinue KADCYLA.

    • Overview
      This image shows a Kaplan-Meier curve of overall survival (OS) in KATHERINE.

      Data
      Overall survival, the second interim endpoint, was significantly higher among patients who received KADCYLA than among those who received trastuzumab (hazard ratio, 0.66 (95% CI: 0.51-0.87; P=0.0027). 7-year OS was 89.1% in the KADCYLA group, compared to 84.4% in the trastuzumab group, representing a 34% reduction in the risk of death.

    • This image shows subgroup analysis of invasive disease-free survival, presented as a forest plot.

    • This image shows the 3-year subgroup analysis of invasive disease-free survival, presented as a forest plot.

    • This image shows the 7-year subgroup analysis of invasive disease-free survival, presented as a forest plot.

    • This image shows the components of KADCYLA:

      Trastuzumab-monoclonal antibody1

      • Selectively binds to HER2

      MCC-stable linker1,3

      • Stabilizes KADCYLA in circulation to release DM1 after entering the target cell

      DM1 cytotoxic agent1,4

      • Approximately 20 to 200 times more potent than taxanes and vinca alkaloids
      • Provides cytotoxicity previously unavailable for clinical use

    • Overview
      This image shows the trial design of EMILIA.

      Details
      EMILIA was a randomized, open-label, international trial involving 991 patients with HER2+, unresectable, locally advanced or metastatic breast cancer who previously received trastuzumab and a taxane (separately or in combination). Inclusion criteria included progression during or after the most recent treatment for locally advanced or metastatic disease or within 6 months after treatment for early-stage disease. Four hundred ninety-five patients were randomized to 21-day cycles of 3.6 mg/kg IV of KADCYLA on day 1. Four hundred ninety-six patients were randomized to 1,250 mg of lapatinib by mouth once daily, and 1,000 mg/m² of capecitabine by mouth twice daily on days 1-14. Treatment continued until disease progression or unacceptable toxicity.

    • Overview
      This image shows the trial design of TH3RESA.

      Details
      TH3RESA was a phase 3, randomized, multicenter, open-label trial of 602 patients with HER2+ advanced breast cancer (ABC). Patients were required to have had disease progression after treatment with ≥2 prior HER2-directed therapies for ABC and prior treatment with trastuzumab, lapatinib, and a taxane. Patients were randomized to 3.6 mg/kg IV of KADCYLA or treatment of physician’s choice (TPC)* per local practice, with 404 patients in the KADCYLA arm and 198 patients in the TPC arm. Patients in the TPC arm who had disease progression had the option to cross over to the KADCYLA arm, and 93 patients did so.

    • Overview
      This image shows overall survival (OS) results for EMILIA.

      Data
      KADCYLA significantly increased median OS (30.9 months, vs 25.1 months with lapatinib + capecitabine—a nearly 6-month improvement in median OS; hazard ratio for death from any cause, 0.68; 95% confidence interval, 0.55 to 0.85; P=0.0006).

    • Overview
      This image shows progression-free survival (PFS) results for EMILIA.

      Data
      Treatment with KADCYLA significantly improved PFS as assessed by independent review (median survival, 9.6 months, vs 6.4 months with lapatinib + capecitabine—a 50% improvement in median PFS; stratified hazard ratio for progression or death from any cause, 0.65; 95% confidence interval, 0.55 to 0.77; P<0.0001).

    • Overview
      This image shows objective response rate (ORR) results for EMILIA.

      Data
      Patients treated with KADCYLA had a higher ORR (43.6%, vs 30.8% with lapatinib + capecitabine—a 12.7% improvement in ORR; 95% confidence interval, 6.0-19.4%).

    • Overview
      This image shows duration of response (DoR) results for EMILIA.

      Data
      Treatment with KADCYLA significantly improved DoR (median DoR, 12.6 months, vs 6.5 months with lapatinib + capecitabine—nearly doubling DoR; 95% confidence interval, 8.4-20.8).

    • Overview
      This image shows overall survival (OS) in patients with central nervous system (CNS) metastases at baseline in EMILIA.

      Data
      The estimated median OS was 26.8 months with KADCYLA vs 12.9 months with lapatinib + capecitabine.

    • Overview
      This image shows progression-free survival (PFS) by independent review committee (IRC) in patients with central nervous system (CNS) metastases at baseline in EMILIA.

      Data
      The estimated median PFS was 5.9 months with KADCYLA vs 5.7 months with lapatinib + capecitabine.

    • Overview
      This image shows progression-free survival (PFS) by investigator results for TH3RESA.

      Data
      Median PFS with KADCYLA was 6.2 months, vs 3.3 months with treatment of physician’s choice (TPC). Stratified HR=0.528; 95% confidence interval, 0.422 to 0.661; P<0.0001.

    • Overview
      This image shows overall survival (OS) results for TH3RESA in the ITT population.

      Data
      Median OS with KADCYLA was 22.7 months, vs 15.8 months with treatment of physician’s choice (TPC). Stratified HR=0.68; 95% confidence interval, 0.54 to 0.85; P=0.0007.

    • Overview
      This image shows the most common severe (Grade ≥3) adverse reactions in EMILIA.

      Data
      Numerical values presented on the image:

      Grade ≥3 nausea seen in 0.8% of KADCYLA patients, compared to 2.5% of lapatinib + capecitabine patients

      Grade ≥3 fatigue seen in 2.5% of KADCYLA patients, compared to 3.5% of lapatinib + capecitabine patients

      Grade ≥3 thrombocytopenia seen in 15% of KADCYLA patients, compared to 0.4% of lapatinib + capecitabine patients

      Grade ≥3 increased transaminases seen in 8.0% of KADCYLA patients, compared to 2.5% of lapatinib + capecitabine patients

      Grade ≥3 diarrhea seen in 1.6% of KADCYLA patients, compared to 21% of lapatinib + capecitabine patients

      Grade ≥3 peripheral neuropathy seen in 2.2% of KADCYLA patients, compared to 0.2% of lapatinib + capecitabine patients

      Grade ≥3 vomiting seen in 0.8% of KADCYLA patients, compared to 4.5% of lapatinib + capecitabine patients

      Grade ≥3 anemia seen in 4.1% of KADCYLA patients, compared to 2.5% of lapatinib + capecitabine patients

      Grade ≥3 stomatitis seen in 0.2% of KADCYLA patients, compared to 2.5% of lapatinib + capecitabine patients

      Grade ≥3 hypokalemia seen in 2.7% of KADCYLA patients, compared to 4.7% of lapatinib + capecitabine patients

      Grade ≥3 neutropenia seen in 2.0% of KADCYLA patients, compared to 4.3% of lapatinib + capecitabine patients

    • This image shows recommended dosing for KADCYLA: 3.6 mg/kg every 3 weeks.

    • Overview
      This image shows the infusion schedule for KADCYLA in metastatic breast cancer.

      Details
      The initial infusion of KADCYLA in EBC takes 90 minutes plus an observation time of at least 90 minutes to monitor for infusion-related reactions. If prior infusions were well tolerated, subsequent infusions take 30 minutes plus an observation time of at least 30 minutes.

      Treat until disease progression or unmanageable toxicity.

    • Overview
      This image shows the dose reduction schedule for adverse reactions to KADCYLA.

      Details
      The starting dose for KADCYLA is 3.6 mg/kg. The first dose reduction for KADCYLA is 3 mg/kg. The second dose reduction for KADCYLA is 2.4 mg/kg. After that, discontinue KADCYLA.