PERJETA (pertuzumab) FOR TREATMENT OF MALIGNANCIES Non-Discrimination Statement and Multi-Language Interpreter Services information are located at the end of this document. Coverage for services, procedures, medical devices and drugs are dependent upon benefit eligibility as outlined in the member's specific benefit plan. This Medical Coverage Guideline must be read in its entirety to determine coverage eligibility, if any. This Medical Coverage Guideline provides information related to coverage determinations only and does not imply that a service or treatment is clinically appropriate or inappropriate. The provider and the member are responsible for all decisions regarding the appropriateness of care. Providers should provide BCBSAZ complete medical rationale when requesting any exceptions to these guidelines. The section identified as Description defines or describes a service, procedure, medical device or drug and is in no way intended as a statement of medical necessity and/or coverage. The section identified as Criteria defines criteria to determine whether a service, procedure, medical device or drug is considered medically necessary or experimental or investigational. State or federal mandates, e.g., FEP program, may dictate that any drug, device or biological product approved by the U.S. Food and Drug Administration (FDA) may not be considered experimental or investigational and thus the drug, device or biological product may be assessed only on the basis of medical necessity. Medical Coverage Guidelines are subject to change as new information becomes available. For purposes of this Medical Coverage Guideline, the terms "experimental" and "investigational" are considered to be interchangeable. BLUE CROSS, BLUE SHIELD and the Cross and Shield Symbols are registered service marks of the Blue Cross and Blue Shield Association, an association of independent Blue Cross and Blue Shield Plans. All other trademarks and service marks contained in this guideline are the property of their respective owners, which are not affiliated with BCBSAZ. O915.6.docx Page 1 of 9
Description: Perjeta (pertuzumab) is a monoclonal antibody that is a human epidermal growth factor receptor 2 (HER2) antagonist. The combination of two HER2-active agents targeting different subdomains of HER2 (pertuzumab targets subdomain II and trastuzumab targets subdomain IV) may result in a more comprehensive blockade of HER2 and its pathways, and thus may lead to greater treatment effect. Perjeta (pertuzumab) is FDA approval for treatment of HER2-positive, metastatic breast cancer and for the treatment of early stage HER2-positive breast cancer as neoadjuvant treatment or as adjuvant treatment. Criteria: Off-label use of a prescription drug for the treatment of cancer may be eligible for coverage. See BCBSAZ Medical Coverage Guideline #O603, Prescription Medications for the Treatment of Cancer. See Resources section for FDA-approved dosage. Perjeta (pertuzumab) for the treatment of HER2-positive breast cancer is considered medically necessary with documentation of ALL of the following: 1. ONE of the following: Metastatic breast cancer (MBC) in an individual who has not received prior anti-her2 therapy or chemotherapy for metastatic disease, used in combination with trastuzumab and docetaxel Early breast cancer, in combination with trastuzumab and chemotherapy, as ONE of the following: a. Neoadjuvant treatment of cancer that is locally advanced, inflammatory or early stage (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen b. Adjuvant treatment of cancer at high risk for recurrence 2. Absence of hypersensitivity to pertuzumab or to any pertuzumab excipients 3. Cardiac function evaluation (echocardiogram or MUGA scan) prior to initiation of therapy and close monitoring during therapy 4. Individual of child bearing potential is on effective contraception prior to initiation of therapy and up to 7 months following the last dose 5. Verification of pregnancy status prior to initiation of therapy O915.6.docx Page 2 of 9
Criteria: (cont.) Continuation of Perjeta (pertuzumab) is considered medically necessary with documentation of ALL of the following: 1. NO unacceptable or unmanageable toxicity from Perjeta (pertuzumab) 2. NO disease recurrence Perjeta (pertuzumab) for all other indications not previously listed or if above criteria not met is considered experimental or investigational based upon: 1. Insufficient scientific evidence to permit conclusions concerning the effect on health outcomes, and 2. Insufficient evidence to support improvement of the net health outcome, and 3. Insufficient evidence to support improvement of the net health outcome as much as, or more than, established alternatives, and 4. Insufficient evidence to support improvement outside the investigational setting. These indications include, but are not limited to: Treatment with dosing or frequency outside the FDA-approved dosing and frequency HER2-positive gastric, colorectal, non-small cell lung and ovarian cancers HER2-positive cancers of the gastro-esophageal junction HER2-negative cancers Resources: Literature reviewed 04/09/18. We do not include marketing materials, poster boards and nonpublished literature in our review. The BCBS Association Medical Policy Reference Manual (MPRM) policy is included in our guideline review. References cited in the MPRM policy are not duplicated on this guideline. 1. 5.01.20 BCBS Association Medical Policy Reference Manual. Pertuzumab for Treatment of Malignancies. Re-issue date 10/12/2017, Issue date 12/13/2012. O915.6.docx Page 3 of 9
Resources: (cont.) Perjeta Package Insert: - FDA-approved indication and dosage: Indication Metastatic Breast Cancer (MBC) Recommended Dose MBC: For intravenous infusion only. Do not administer as an intravenous push or bolus. Administer Perjeta, trastuzumab and docetaxel by intravenous infusion every 3 weeks. The initial Perjeta dose is 840 mg administered as a 60-minute intravenous infusion, followed every 3 weeks thereafter by 420 mg administered as a 30 to 60 minute intravenous infusion. Dose reductions of Perjeta are not recommended. When administered with Perjeta, the recommended initial dose of trastuzumab is 8 mg/kg administered as a 90-minute intravenous infusion, followed every 3 weeks by a dose of 6 mg/kg administered as an intravenous infusion over 30 to 90 minutes. Perjeta should be discontinued if trastuzumab treatment is discontinued. When administered with Perjeta, the initial dose of docetaxel is 75mg/m 2 administered as an intravenous infusion. The dose may be escalated to 100mg/m 2 administered every 3 weeks if the initial dose is well tolerated. Perjeta, trastuzumab, and taxane (docetaxel) should be administered sequentially. Perjeta and trastuzumab can be given in any order. Taxane (docetaxel) should be administered after Perjeta and trastuzumab. An observation period of 30 to 60 minutes is recommended after each Perjeta infusion and before commencement of any subsequent infusion of trastuzumab or taxane (docetaxel). O915.6.docx Page 4 of 9
Resources: (cont.) Perjeta Package Insert: (cont.) - FDA-approved indication and dosage: (cont.) Indication Neoadjuvant Treatment of Early Breast Cancer Recommended Dose Neoadjuvant: Perjeta should be administered every 3 weeks for 3 to 6 cycles as part of one of the following treatment regimens for early breast cancer: 1. Four preoperative cycles of Perjeta in combination with trastuzumab and docetaxel followed by 3 postoperative cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) as given in NeoSphere Study 2. Three or four preoperative cycles of FEC alone followed by 3 or 4 preoperative cycles of Perjeta in combination with docetaxel and trastuzumab as given in TRYPHARNA and BERENICE Studies 3. Six preoperative cycles of Perjeta in combination with docetaxel, carboplatin, and trastuzumab (TCH) (escalation of docetaxel above 75mg/m2 is not recommended) as given in TRYPHARNA Study 4. Four preoperative cycles of dose-dense doxorubicin and cyclophosphamide (ddac) alone followed by 4 preoperative cycles of Perjeta in combination with paclitaxel and trastuzumab as given in BERENICE Study. Following surgery, individuals should continue to receive Perjeta and trastuzumab to complete 1 year of treatment (up to 18 cycles) The initial Perjeta dose is 840 mg administered as a 60-minute intravenous infusion, followed every 3 weeks thereafter by 420 mg administered as a 30 to 60 minute intravenous infusion. Dose reductions of Perjeta are not recommended. When administered with Perjeta, the recommended initial dose of trastuzumab is 8 mg/kg administered as a 90-minute intravenous infusion, followed every 3 weeks by a dose of 6 mg/kg administered as an intravenous infusion over 30 to 90 minutes. Perjeta should be discontinued if trastuzumab treatment is discontinued. When administered with Perjeta, the initial dose of docetaxel is 75mg/m 2 administered as an intravenous infusion. The dose may be escalated to 100mg/m 2 administered every 3 weeks if the initial dose is well tolerated and as per protocol used. O915.6.docx Page 5 of 9
Resources: (cont.) Perjeta Package Insert: (cont.) - FDA-approved indication and dosage: (cont.) Indication Neoadjuvant Treatment of Early Breast Cancer (cont.) Recommended Dose Perjeta, trastuzumab, and taxane (docetaxel, paclitaxel) should be administered sequentially. Perjeta and trastuzumab can be given in any order. Taxane (docetaxel, paclitaxel) should be administered after Perjeta and trastuzumab. An observation period of 30 to 60 minutes is recommended after each Perjeta infusion and before commencement of any subsequent infusion of trastuzumab or taxane (docetaxel, paclitaxel). In individuals receiving an anthracycline-based regimen, Perjeta and trastuzumab should be administered following completion of the anthracycline. Adjuvant Treatment of Early Breast Cancer at High Risk of Recurrence PERJETA should be administered in combination with trastuzumab every 3 weeks for a total of 1 year (up to 18 cycles) or until disease recurrence or unmanageable toxicity, whichever occurs first, as part of a complete regimen for early breast cancer, including standard anthracycline- anthracycline and/or taxane-based chemotherapy as given in APHINITY Study. PERJETA and trastuzumab should start on Day 1 of the first taxane-containing cycle. The initial Perjeta dose is 840 mg administered as a 60-minute intravenous infusion, followed every 3 weeks thereafter by 420 mg administered as a 30 to 60 minute intravenous infusion. Dose reductions of Perjeta are not recommended. When administered with Perjeta, the recommended initial dose of trastuzumab is 8 mg/kg administered as a 90-minute intravenous infusion, followed every 3 weeks by a dose of 6 mg/kg administered as an intravenous infusion over 30 to 90 minutes. Perjeta should be discontinued if trastuzumab treatment is discontinued. Perjeta, trastuzumab, and taxane should be administered sequentially. Perjeta and trastuzumab can be given in any order. Taxane should be administered after Perjeta and trastuzumab. An observation period of 30 to 60 minutes is recommended after each Perjeta infusion and before commencement of any subsequent infusion of trastuzumab or taxane. In individuals receiving an anthracycline-based regimen, Perjeta and trastuzumab should be administered following completion of the anthracycline. O915.6.docx Page 6 of 9
Resources: (cont.) Initial Approval Duration: For MBC & EBC: 6 months Renewal Approval Duration: For MBC: 12 months For EBC: 6 month (for up to 18 cycles) O915.6.docx Page 7 of 9
Non-Discrimination Statement: Blue Cross Blue Shield of Arizona (BCBSAZ) complies with applicable Federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability or sex. BCBSAZ provides appropriate free aids and services, such as qualified interpreters and written information in other formats, to people with disabilities to communicate effectively with us. BCBSAZ also provides free language services to people whose primary language is not English, such as qualified interpreters and information written in other languages. If you need these services, call (602) 864-4884 for Spanish and (877) 475-4799 for all other languages and other aids and services. If you believe that BCBSAZ has failed to provide these services or discriminated in another way on the basis of race, color, national origin, age, disability or sex, you can file a grievance with: BCBSAZ s Civil Rights Coordinator, Attn: Civil Rights Coordinator, Blue Cross Blue Shield of Arizona, P.O. Box 13466, Phoenix, AZ 85002-3466, (602) 864-2288, TTY/TDD (602) 864-4823, crc@azblue.com. You can file a grievance in person or by mail or email. If you need help filing a grievance BCBSAZ s Civil Rights Coordinator is available to help you. You can also file a civil rights complaint with the U.S. Department of Health and Human Services, Office for Civil Rights electronically through the Office for Civil Rights Complaint Portal, available at https://ocrportal.hhs.gov/ocr/portal/lobby.jsf, or by mail or phone at: U.S. Department of Health and Human Services, 200 Independence Avenue SW., Room 509F, HHH Building, Washington, DC 20201, 1 800 368 1019, 800 537 7697 (TDD). Complaint forms are available at http://www.hhs.gov/ocr/office/file/index.html Multi-Language Interpreter Services: O915.6.docx Page 8 of 9
Multi-Language Interpreter Services: (cont.) O915.6.docx Page 9 of 9