Prior Auth Protocol

FDA Approved Indications:

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.

Health Net Approved Indications and Usage Guidelines:

Diagnosis of HER2-positive recurrent or metastatic breast cancer

AND

Failure or clinically significant adverse effects to prior therapy (in combination or separately) including a taxane and Herceptin^R(trastuzumab) [see General Information for examples].

Coverage is Not Authorized For:

Non-FDA approved indications, which are not listed in the Health Net Approved Indications and Usage Guidelines section, unless there is sufficient documentation of efficacy and safety in the published literature.

General Information:

Kadcyla has a black box warning for hepatoxicity, cardiac toxicity, and embryo-fetal toxicity. It is recommended to monitor liver function prior to initiation and prior to each dose. Institute dose modifications or permanently discontinue as appropriate. Kadcyla may also lead to reductions in left ventricular ejection fraction (LVEF). Assess LVEF prior to initiation. Monitor and withhold dosing or discontinue as appropriate.
Do not substitute Kadcyla for or with Herceptin.
Failure of preferred agents is defined by disease progression while being treated with those agents (e.g. taxanes, and Herceptin).
Taxanes include paclitaxel (Taxol^R), albumin-bound paclitaxel (Abraxane^R) and docetaxel (Taxotere^R).
Per NCCN for Metastatic breast cancer with HER2 overexpression and Nonadjuvant pertuzumab is used with trastuzumab and docetaxel has a class 2A recommendation.
Either an immunohistochemistry (IHC) assay or a fluorescence in situ hybridization (FISH) assay can be used to make an initial assessment of HER2 tumor status.
Patients treated with Kadcyla had a median progression-free survival of 9.6 months vs. 6.4 months in patients treated with lapatinib plus capecitabine. The median overall survival was 30.9 months and 25.1 months in the two groups, respectively.

Therapeutic Alternatives:

Drug	Dosing Regimen	Dose Limit/ Maximum Dose
Preferred Adjuvant Chemotherapy Regimen for HER2 positive metastatic breast cancer: doxorubicin/cyclophosphamide followed by paclitaxel + Herceptin docetaxel followed by carboplatin + Herceptin Other Adjuvant Regimens: docetaxel + Herceptin followed by fluorouracil/epirubicin/ cyclophosphamide doxorubicin/cyclophosphamide followed by docetaxel + Herceptin pertuzumab + Herceptin + docetaxel Neoadjuvant Regimen: paclitaxel + Herceptin followed by cyclophosphamide/epirubicin/ fluorouracil + Herceptin pertuzumab + Herceptin + docetaxel Preferred Chemotherapy Regimens for recurrent or metastatic breast cancer: carboplatin/paclitaxel + Herceptin paclitaxel + Herceptin docetaxel + Herceptin vinorelbine + Herceptin capecitabine + Herceptin	Various dosing regimens	Number of cycles varies

Preferred Adjuvant Chemotherapy Regimen for HER2 positive metastatic breast cancer:

doxorubicin/cyclophosphamide followed by paclitaxel + Herceptin
docetaxel followed by carboplatin + Herceptin

Other Adjuvant Regimens:

docetaxel + Herceptin followed by fluorouracil/epirubicin/ cyclophosphamide
doxorubicin/cyclophosphamide followed by docetaxel + Herceptin
pertuzumab + Herceptin + docetaxel

Neoadjuvant Regimen:

paclitaxel + Herceptin followed by cyclophosphamide/epirubicin/ fluorouracil + Herceptin
pertuzumab + Herceptin + docetaxel

Preferred Chemotherapy Regimens for recurrent or metastatic breast cancer:

carboplatin/paclitaxel + Herceptin
paclitaxel + Herceptin
docetaxel + Herceptin
vinorelbine + Herceptin
capecitabine + Herceptin

Various dosing regimens

Number of cycles varies

* Requires Prior Authorization

Recommended Dosing Regimen and Authorization Limit:

Drug	Dosing Regimen	Authorization Limit
Kadcyla	3.6 mg/kg IV infusion every 3 weeks (21-day cycle). Do not administer Kadcyla at doses greater than 3.6 mg/kg.	6 months or to member's renewal period, whichever is sooner. Treatment continues until no longer clinically beneficial or until unacceptable toxicity occurs.

Product Availability:

Vial: Single-use vials containing 100 mg or 160 mg per vial.

References:

1. Kadcyla [Prescribing Information]. South San Francisco, CA: Genentech, Inc.; May 2013.

2. National Comprehensive Cancer Network (NCCN) Practice Guidelines in Oncology; Breast Cancer Version 1.2013, available at http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf., Accessed June 16, 2014..

3. Clinical Pharmacology Web site. Available at http://www.clinicalpharmacology-ip.com/default.aspx, Accessed July 1, 2014.

4. Micromedex^R Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed July 1,2014.

5. Kadcyla. American Hospital Formulary Service Drug Information. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed July 1, 2014.

6. Verma S, Miles D, Gianni L, et al. EMILIA study group trastuzumab emtansine for HER2-positive advanced breast cancer. The New England Journal of Medicine 2012 Nov 8;367(19):1783-91.

7. Perjeta [Prescribing Information]. South San Francisco, CA: Gentech, Inc.; September 2013.