CLINICAL POLICY Department: Medical Management Document Name: HER2 Breast Cancer Treatments

Transcription

1 Page: 1 of 11 Specialist Review: Revised: 06/13 IMPORTANT REMINDER This Clinical Policy has been developed by appropriately experienced and licensed health care professionals based on a thorough review and consideration of generally accepted standards of medical practice, peer-reviewed medical literature, government agency/program approval status, and other indicia of medical necessity. The purpose of this Clinical Policy is to provide a guide to medical necessity. Benefit determinations should be based in all cases on the applicable contract provisions governing plan benefits ( Benefit Plan Contract ) and applicable state and federal requirements, as well as applicable plan-level administrative policies and procedures. To the extent there are any conflicts between this Clinical Policy and the Benefit Plan Contract provisions, the Benefit Plan Contract provisions will control. Clinical policies are intended to be reflective of current scientific research and clinical thinking. This Clinical Policy is not intended to dictate to providers how to practice medicine, nor does it constitute a contract or guarantee regarding payment or results. Providers are expected to exercise professional medical judgment in providing the most appropriate care, and are solely responsible for the medical advice and treatment of members. Subject: Prior authorization for Herceptin (trastuzumab), Kadcyla (ado-trastuzumab emtansine, and Perjeta (pertuzumab) Description: The intent of the criteria is to ensure that patients follow selection elements established by Centene medical policy for Herceptin and Kadcyla and Perjeta. FDA-Approved Indications -2 Brand Generic Indications Name Name Herceptin trastuzumab HER2-Positive Breast Cancer Adjuvant treatment in combination with or following chemotherapy (Appendix C) Metastatic disease as a single agent in patients who received prior chemotherapy for metastatic disease 1 Recurrent or metastatic disease in combination with chemotherapy 1 HER2-Positive Esophageal, Gastroesophageal Junction, or Gastric Cancer Advanced or metastatic disease in combination with chemotherapy 1,

2 Page: 2 of 11 Specialist Review: Revised: 06/13 Kadcyla adotrastuzumab emtansine HER2-Positive Breast Cancer Metastatic disease as a single agent in patients 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. 2 Perjeta Pertuzumab For use in combination with trastuzumab and docetaxel for the treatment of patients with (HER) 2-positive metastatic breast cancer who have not received prior anti-her2 therapy or chemotherapy for metastatic disease. Use in combination with trastuzumab and docetaxel as neoadjuvant treatment of patients with HER2 positive, locally advanced, inflammatory, or early stage breast cancer either greater than 2cm in diameter or node positive as part of a complete treatment regimen for early breast cancer. Policy/Criteria: It is the policy of Health Plans affiliated with Centene Corporation that Herceptin, Kadcyla and Perjeta are medically necessary for members who meet the following algorithm criteria: Figure 1. Herceptin Algorithm Figure 2. Kadcyla Algorithm Figure 3. Perjeta Algorithm

3 Page: 3 of 11 Specialist Review: Revised: 06/13 Figure 1. Herceptin Algorithm Currently receiving Herceptin? Continuing to benefit from Herceptin therapy? HER2 positive disease? Experiencing unmanageable toxicity from Herceptin therapy? (Appendix G) What is the diagnosis? Breast cancer Metastatic gastric or GE junction cancer Other What is the intent of treatment? Treatment of Metastatic disease Received previous chemotherapy and/or anti-her-2 therapy for metastasis? Received prior treatment for metastatic disease?? Adjuvant treatment Approve for 6 months Currently receiving Herceptin through a Centene benefit? Approve up to total 52 weeks Being used with paclitaxel as a first-line therapy? Used in combination with cisplatin and capecitabine or 5- fluorouracil? Is the breast cancer nodenegative? Is the breast cancer ER/PR negative? Is Herceptin being used with chemotherapy? (See Appendix C) Being used as a single agent following multimodality anthracycline based therapy? Is the breast cancer associated with a high risk feature? (see Appendix B) Currently receiving Herceptin therapy? Approve for 6 months Approve up to total 52 weeks

4 Page: 4 of 11 Specialist Review: Revised: 06/13 Figure 2. Kadcyla Algorithm What is the diagnosis? Metastatic breast cancer HER-2 positive disease? Other Previously received Herceptin and a taxane (either separately or in combination) for a metastatic disease? Disease recurrence during or within six months of completing adjuvant therapy? Being used as a single agent? Currently receiving Kadcyla? Document baseline transaminase, total Bili and LVEF Disease progression or unmanageable toxicity (App E) since starting Kadcyla? What is the patient s current LVEF? Experienced 10% absolute decrease in LVEF from pretreatment values? 40% < 40% Current platelet count? < 50,000 mm 3 50,000/mm 3 Approve 6 months

5 Page: 5 of 11 Specialist Review: Revised: 06/13 Figure 3: Perjeta Algorithm Is the patient s breast cancer metastatic? Will it be used prior to surgery? yes Is the breast cancer locally advanced, inflammatory or early stage? yes no yes no Received prior anti-her2 therapy (See Appendix A) or chemotherapy for metastatic disease? no Being used in combination with trastuzumab and docetaxel? yes Does/did the patient have HER2- positive disease? no Experiencing disease progression or unacceptable toxicity? Is the patient currently receiving Perjeta? Approve for 6 months Background Breast cancer is the most common cancer in women and is second only to lung cancer as a cause of cancer death. 5 The American Cancer Society estimates that 234,580 new cases of breast cancer and 40,030 breast cancer-related deaths will occur in the United States in Although most patients present with an early stage of breast cancer initially, about 6% to 10% of patients present with metastatic breast cancer. 7 While metastatic breast cancer cannot be cured, therapy focuses on prolonging survival, maintaining quality of life, and delaying disease progression. The median survival for metastatic breast cancer is approximately 18 to 30 months. Treatment options for metastatic breast cancer include endocrine therapy (e.g., tamoxifen, letrozole), chemotherapy (e.g., anthracyclines, taxanes), and targeted agents, such as HER2 targeted agents (i.e., trastuzumab, lapatinib) and angiogenesis inhibitors (i.e., bevacizumab). 7,8

6 Page: 6 of 11 Specialist Review: Revised: 06/13 The selection of therapy is based on a number of disease-related and patient-related factors which include tumor biology (hormonal receptors, HER2 status), disease-free interval, previous therapies and response, tumor burden (number and site of metastases), comorbidities, menopausal status, patient s age, need for rapid disease/symptom control, and patient preferences. Evaluation of HER2 overexpression is important as it is associated with increased rates of recurrence, tumor aggressiveness, and decreased overall survival. 7 Of note, approximately 20% of breast cancers have increased amounts of the HER2 protein. Herceptin is a recombinant DNA-derived humanized anti-her2 monoclonal antibody. 1 Herceptin is indicated for the treatment of HER2 overexpressing breast cancer and for the treatment of HER2 overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma. Herceptin also has a compendial use for the treatment of esophageal cancer. 1 Kadcyla is a HER2-targeted antibody and microtubule inhibitor conjugate. 2 The antibody component is trastuzumab and the microtubule inhibitor is the small molecule cytotoxin, DM1. Binding of DM1 to tubulin disrupts microtubule networks in the cell resulting in cell cycle arrest and apoptotic cell death. 2 Similar to Herceptin, Kadcyla has shown to inhibit HER2 receptor signaling, mediate antibody-dependent cell-mediated cytotoxicity and inhibit shedding of the HER2 extracellular domain in human breast cancer cells that overexpress HER2 in vitro. 2 Kadcyla is indicated, as a single agent, for the treatment of patients with HER2-positive metastatic breast cancer who previously received trastuzumab and a taxane separately or in combination. 2 Patients should have either received prior therapy for metastatic disease, or developed disease recurrence during or within six months of completing adjuvant therapy. 2 Kadcyla cannot be substituted for or with trastuzumab. 2 The recommended dose of Kadcyla is 3.6 mg/kg infused intravenously over 90 minutes every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity. Kadcyla should not be administered at doses greater than 3.6 mg/kg nor re-escalated after a dose reduction has been made. Patients should be observed during the infusion and for at least 90 minutes following the initial dose for fever, chills, or other infusion-related reactions. For subsequent infusions, Kadcyla may be administered over 30 minutes if prior infusions were well tolerated. Patients should be observed during the infusion and for at least 30 minutes after infusion. Perjeta is a recombinant humanized monoclonal antibody that is believed to work by targeting a different part of the HER-protein than trastuzumab, resulting in further reduction in growth and survival for HER2-positive breast cancer cells. 4,9 The safety and efficacy of Perjeta were evaluated in a randomized, double-blind, placebo-controlled trial enrolling a total of 808 patients with HER2-positive metastatic breast cancer. 10 Patients were randomly assigned to receive trastuzumab plus docetaxel and either Perjeta or placebo. The primary endpoint was progression-free survival (PFS). The results showed that patients treated with the combination of

7 Page: 7 of 11 Specialist Review: Revised: 06/13 Perjeta, trastuzumab, plus docetaxel had a median PFS of 18.5 months. Those treated with trastuzumab, docetaxel, plus placebo combination experienced a PFS of 12.4 months. Perjeta can cause fetal harm when administered to a pregnant woman. 4 Assessment of left ventricular ejection fraction (LVEF) prior to initiation of Perjeta treatment and at regular intervals (e.g., every three months) during treatment to ensure that LVEF is within the institution s normal limits is recommended. If LVEF is < 40% or is 40% to 45% within a 10% or greater absolute decrease below the pretreatment value, Perjeta plus trastuzumab should be withheld and LVEF assessment should be repeated within approximately 3 weeks. Perjeta plus trastuzumab should be discontinued if the LVEF has not improved or has declined further, unless the benefits outweigh the risks. Monitor for signs and symptoms of infusion related reactions; if a significant infusion associated reaction occurs, slow or interrupt the infusion and administer appropriate medical therapies. The most common adverse reactions in patients treated with Perjeta, trastuzumab, plus docetaxel included diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral neuropathy. Exposure to Perjeta can result in embryo-fetal death and birth defects. Studies in animals have resulted in oligohydramnios, delayed renal development, and death. Patients should be advised of these risks and the need for effective contraception. Safety A major component of this policy is to ensure necessary safety concerns are addressed prior to initiating therapy with Herceptin or Kadcyla. Information from the product labeling, U.S. Food and Drug Administration MedWatch, and primary literature are considered. Safety concerns for trastuzumab-containing agents are summarized in Table 2. Table 2. Safety Concerns for Herceptin and Kadcyla 1,2 Safety Concern Herceptin Kadcyla Arrhythmias, hypertension, cardiac failure, cardiomyopathy, and cardiac death X* Left ventricular dysfunction X* X* Infusion reactions and pulmonary toxicity (eg, anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory X* X distress syndrome) Exposure during pregnancy can result in embryo-fetal death or birth defects X* X* Exacerbation of chemotherapy-induced neutropenia X Hepatotoxicity X* Hypersensitivity reactions X Thrombocytopenia X

8 Page: 8 of 11 Specialist Review: Revised: 06/13 Neurotoxicity Extravasation X = yes; * Boxed warnings X X Table 3: Dose Reduction schedule for Kadcyla Dose Reduction Schedule Dose Level Starting dose reduction 3.6 mg/kg First dose reduction 3 mg/kg Second dose reduction 2.4 mg/kg Requirement for further dose reduction Discontinue treatment Herceptin can cause asymptomatic decline in left ventricular ejection fraction (LVEF) and has been associated with left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death. Therefore, LVEF is assessed prior to initiation of Herceptin and at regular intervals during treatment. Herceptin dosing is withheld for at least 4 weeks for either of the following: Greater than or equal to 16% absolute decrease in LVEF from pre-treatment vales or LVEF below institutional limits of normal and greater than or equal to 10% absolute decrease in LVEF from pretreatment values. Herceptin may be resumed if, within 4-8 weeks, the LVEF returns to normal limits and the absolute decrease from baseline is </= 15%. The use of Herceptin may also induce fetal harm so it is vital to advise women of childbearing age and potential to use contraception. Herceptin use can also result in serious and fatal pulmonary toxicity such as, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, noncardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, acute respiratory distress syndrome, and pulmonary fibrosis. Such events can occur as a result of infusion reactions. It is recommended to discontinue Herceptin for severe or life-threatening infusion reactions manifesting as anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome. If severe or life threatening infusion reactions, Herceptin should be discontinued. It may also be necessary to interrupt the infusion in patients with dyspnea or clinically significant hypotension. Kadcyla has been shown to cause hepatotoxicity in the form of asymptomatic, transient increases in serum transaminases. Monitoring serum transaminases and bilirubin prior to initiation of Kadcyla treatment and prior to each dose is recommended. Kadcyla also puts patients at increased risk of developing left ventricular dysfunction. A decrease in LVEF < 40% was seen in patients treated with Kadcyla. Assessing LVEF prior to initiation and at regular intervals (e.g, every three months) during treatment is recommended to ensure LVEF is within normal limits. Management of increased serum transaminases, hyperbilirubinemia, left ventricular dysfunction, thrombocytopenia, pulmonary toxicity or peripheral neuropathy may require temporary

9 Page: 9 of 11 Specialist Review: Revised: 06/13 interruption. Proper dose reductions and/or treatment discontinuation of Kadcyla are provided in appendixes D, E and F as per guidelines. Appendices Appendix A. Abbreviations ARDS = acute respiratory distress syndrome ALT = alanine aminotransferase AST = aspartate aminotransferase ER/PR = estrogen receptor/progesterone receptor GE = gastroesophageal HER = human epidermal growth factor receptor LVEF = left ventricular ejection fraction MUGA = multi-gated acquisition Appendix B. High-risk Features Tumor size > 2 cm Age < 35 years Histologic and/or nuclear Grade 2 or 3 Appendix C. Adjuvant chemotherapy used with Herceptin As part of a treatment regimen consisting of doxorubicin and cyclophosphamide (AC), and either paclitaxel or docetaxel With docetaxel and carboplatin Appendix D: Dose modification guidelines (Refer to table 3) If serum transaminases exceed 5 times but less than or equal to 20 times the upper normal limit, do not administer Kadcyla until AST/ALT levels recover to greater than 2.5 to less than or equal to 5 times the ULN and then reduce one dose level If bilirubin levels are greater than 3 times but less than or equal to 10 times the upper normal limit, do not administer Kadcyla until bilirubin recover to 1.5 but less than or equal to 3 times the upper normal limit and then reduce one dose level If platelet count is very low ( PLT <25,000 mm/^3), recover to Grade 1 ( 75,000/mm^3) and then reduce one dose level. (SIDE NOTE: If PLT is between 25,000 mm^3 to 75,000 mm, but recovers to > 75,000 mm, treat at same dose level, no need to reduce. Appendix E. Conditions to terminate the use of Kadcyla Serum transaminase > 20 times the upper normal limit Bilirubin levels > 10 times the upper normal limit Diagnosed with regenerative hyperplasia (NRH) Diagnosed with interstitial lung disease (ILD) or pneumonitis.

10 Page: 10 of 11 Specialist Review: Revised: 06/13 Symptomatic CHF LVEF < 40% confirmed by repeat assessment within 3 weeks Appendix F. Left Ventricular Ejection Fraction dose modifications in Kadcyla. 2 LVEF 40% to 45% and decrease is 10% points from baseline LVEF 40% to 45% and decrease is <10% points from baseline LVEF > 45% Do not administer Kadcyla. Repeat LVEF assessment within 3 weeks. If the LVEF has not recovered to within 10% points from baseline, discontinue Kadcyla Continue treatment with Kadcyla Repeat LVEF assessment within 3 weeks. Continue treatment with Kadcyla Appendix G: Unmanageable toxicities that require discontinuation of Herceptin Pulmonary toxicity which includes: Dyspnea Interstitial pneumonitis Pulmonary infiltrates pleural effusions n-cardiogenic pulmonary edema Pulmonary insufficiency and hypoxia Acute respiratory distress syndrome Pulmonary fibrosis Severe infusion reactions manifesting as: Anaphylaxis Angioedema Interstitial pneumonitis Acute respiratory distress syndrome. Grade 3-4 neutropenia and of febrile neutropenia LVEF decrease (see Appendix F) References 1. Herceptin [package insert]. South San Francisco, CA: Genentech, Inc.; October Kadcyla [package insert]. South San Francisco, CA: Genentech, Inc.; May National Cancer Comprehensive Network Drugs and Biologics Compendium. Available at: Accessed May 21, Perjeta [package insert]. South San Francisco, CA: Genentech, Inc.; April 2013.

11 Page: 11 of 11 Specialist Review: Revised: 06/13 5. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer. Version Available at: Accessed July 2, American Cancer Society. Cancer Facts and Figures Atlanta GAGC. Available at: acspc pdf. Accessed July 2, Ravnan MC, Ravnan SL, Walberg MP. Metastatic breast cancer: a review of current and novel pharmacotherapy. Formulary. 2011; 46: Cardoso F, Fallowfield L, Costa A et al. Locally recurrent or metastatic breast cancer: European Society for Medical Oncology (ESMO) clinical practice guidelines for diagnosis, treatment and follow-up. Annals of Onc. 2011; 22(Supp 6): FDA News: FDA approves Perjeta for type of late-stage breast cancer. Food and Drug Administration Web site. mpaign=google2&utm_source=fdasearch&utm_medium=website&utm_term=perjeta&utm _content=1. Accessed June 11, Baselga J, Cortés J, Kim S et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012; 366(2): Revision Log Date Added the treatment regimen for use in metastatic breast cancer in combination 07/12 with pertuzumab and docetaxel. Added Kadcyla 06/13 Renamed to HER2 Breast Cancer Treatments 6/14 Removed prospective monitoring question from Figure 1 Added Perjeta and Appendices D-G 2014 Centene Corporation. All rights reserved. All materials are exclusively owned by Centene Corporation and are protected by United States copyright law and international copyright law. part of this publication may be reproduced, copied, modified, distributed, displayed, stored in a retrieval system, transmitted in any form or by any means, or otherwise published without the prior written permission of Centene Corporation. You may not alter or remove any trademark, copyright or other notice contained herein. Centene and Centene Corporation are registered trademarks exclusively owned by Centene Corporation.