Anthem Blue Cross California Kadcyla (ado-trastuzumab) Form

Overview Clinical criteria Overview Coding Document history References This document addresses the use of Kadcyla (ado-trastuzumab). Kadcyla, an antibody-drug conjugate (ADC) that utilizes the HER2- targeting properties of trastuzumab to selectively deliver chemotherapy to HER2-overexpressing tumor cells. This targeted approach minimizes toxicity by limiting exposure of DM1 (N-methyl-N-[3-mercapto-1-oxopropyl]-L-alanine ester of maytansinol) to normal cells. Breast cancer is a type of tumor comprised of malignant (cancerous) cells that start to grow in the breast and may spread (metastasize) to surrounding tissues and other areas of the body (American Cancer Society, 2016). Breast cancer is commonly treated by various modalities which include combinations of surgery, radiation therapy, chemotherapy and hormone therapy (National Cancer Institute, 2019). The prognosis and selection of therapies can be affected by clinical and pathologic features of the tumor. One of these includes the human epidermal growth factor receptor 2 gene ERBB2 which is commonly referred to as HER2. Other names for this gene include NEU, Her-2, HER-2/neu and c-erb B2. Initially the HER2 gene was detected in frozen breast tumor samples. Amplification of the HER2 gene was later correlated to overexpression of protein levels in samples of breast cancer. The FDA approved indication for Kadcyla includes use as a single agent to treat those with HER2-positive, metastatic breast cancer who previously received trastuzumab and/or taxane therapy or had disease recurrence within 6 months of completing adjuvant therapy. The National Comprehensive Cancer Network (NCCN) provides additional recommendations with a category 2A level of evidence for the use of Kadcyla as a preferred option for treatment of individuals with HER2-positive metastatic breast cancer that progresses on first-line trastuzumab-containing regimen. The guidelines do not recommend the use of Kadcyla in the neoadjuvant setting. The updated NCCN guideline provides a category 1 recommendation for use of Kadcyla as a preferred regimen as preferred adjuvant systemic therapy in individuals with HER2+ tumors and locally advanced disease following completion of planned chemotherapy and following mastectomy or lumpectomy. NCCN also provides a level category 2A rating for Kadcyla’s use as single-agent therapy for recurrent or metastatic HER2-positive disease that is HR-negative or HR-positive. NCCN also provides a 2A recommendation for the use in limited or extensive brain metastases in those with HER2 positive breast cancer. In the NCCN clinical practice guideline for Head and Neck cancers the NCCN Panel recommends the use of Kadcyla at a category level 2A rating (previously level 2B rating) in certain circumstances as a single-agent systemic therapy for HER2-positive-recurrent disease with distant metastases or unresectable locoregional recurrence or second primary with prior radiation therapy. At this time the guideline’s discussion section updates are under progress and there are no published trials discussing the recommendation. There is one clinical study in progress under clinicaltrials.gov. Under clinical judgement, the Hematology/Oncology Subcommittee added the use in Salivary Gland tumors. Other Uses In the NCCN clinical practice guideline for non-small cell lung cancer the NCCN Panel now recommends use of Kadcyla (category 2A) in treatment of individuals with HER2 mutations in lung cancer based on recent unpublished data from a small phase 2 basket trial (Li, 2018). The NCCN guidelines for gastric cancer (2019) do not recommend the use of Kadcyla to treat these cancer types. There is a lack of published data from large randomized controlled trials to demonstrate long-term efficacy and safety for these off-label uses. NCCN also provides a 2A recommendation for use in salivary gland tumors. The evidence comes from two basket trials for a total of 13 individuals. At this time, there is a lack of published data from large randomized trials for both efficacy and safety for this off-label use. Definitions and Measures HER2 testing (adapted from American Society of Clinical Oncology/College of American Pathologists): 1 Positive HER2: • • IHC 3+ based on circumferential membrane staining that is complete, intense. (Observed in a homogeneous and contiguous population and within > 10% of the invasive tumor cells). ISH positive based on: o Single-probe average HER2 copy number ≥ 6.0 signals/cell* o Dual-probe HER2/CEP 17 ratio ≥ 2.0* with an average HER2 copy number ≥ 4.0 signals/cell. o Dual-probe HER2/CEP17 ratio ≥ 2.0* with an average HER2 copy number < 4.0 signals/cell. o Dual-probe HER2/CEP17 ratio < 2.0* with an average HER2 copy number ≥ 6.0 signals/cell. *(Observed in a homogeneous and contiguous population and within >10% of the invasive tumor cells. By counting at least 20 cells within the area) Equivocal HER2: • • IHC 2+ based on circumferential membrane staining that is incomplete and/or weak/moderate and within >10% of the invasive tumor cells or complete and circumferential membrane staining that is intense and within ≤10% of the invasive tumor cells. ISH equivocal based on: o Single-probe average HER2 copy number ≥ 4.0 and < 6.0 signals/cell. o Dual-probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number ≥ 4.0 signals/cell. Negative HER2 if a single test (or both tests) performed show: • • IHC 1+ as defined by incomplete membrane staining that is faint/barely perceptible and within > 10% of the invasive tumor cells. IHC 0 as defined by no staining observed or membrane staining that is incomplete and is faint/barely perceptible and within ≤ 10% of the invasive tumor cells. • ISH negative based on: o Single-probe average HER2 copy number < 4.0 signals/cell. o Dual-probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number < 4.0 signals/cell. Metastasis: The spread of cancer from one part of the body to another; a metastatic tumor contains cells that are like those in the original (primary) tumor and have spread. Monoclonal antibody: A protein developed in the laboratory that can locate and bind to specific substances in the body and on the surface of cancer cells. One line of therapy: Single line of therapy. Targeted biologic agent: A newer type of drug developed specifically to target genetic changes in cells that cause cancer. It works differently than standard chemotherapy drugs, often with different side effects. Clinical Criteria When a drug is being reviewed for coverage under a member’s medical benefit plan or is otherwise subject to clinical review (including prior authorization), the following criteria will be used to determine whether the drug meets any applicable medical necessity requirements for the intended/prescribed purpose. Kadcyla (ado-trastuzumab) Requests for Kadcyla (ado-trastuzumab) may be approved if the following criteria are met: I. Individual has a diagnosis of HER2-positive (HER2+) breast cancer (NCCN 1) confirmed by one of the following: A. Immunohistochemistry (IHC) is 3 +; OR In situ hybridization (ISH) positive; B. AND C. Used in one of the following ways: 1. OR 2. Individual has early breast cancer; AND a. b. Individual is using as a single agent; AND Individual is using as adjuvant treatment of early non-metastatic breast cancer for residual invasive disease in the breast or axilla after surgery after receiving at least 6 cycles (16 weeks) of neoadjuvant therapy containing a taxane (with or without anthracycline) and trastuzumab (or trastuzumab biosimilars); Individual has metastatic breast cancer disease; AND Individual is using as a single agent; AND a. 2 b. c. Individual has previously received trastuzumab and a taxane, separately or in combination; AND Individual has either received prior therapy for metastatic disease or developed disease recurrence during or within 6 months of completing adjuvant therapy; Individual has a diagnosis of limited or extensive brain metastases with HER2-positive breast cancer; AND A. Using as initial or primary treatment in asymptomatic disease; OR B. As treatment for recurrent/relapsed disease with stable systemic disease or reasonable systemic treatment options; Individual has a diagnosis of recurrent HER2+ salivary gland tumors (NCCN 2A); AND A. B. Using as single-agent systemic therapy. Individual has had prior anti-HER2+ therapy (e.g. trastuzumab or trastuzumab biosimilars) (Clinical judgement); AND OR II. OR III. Requests for Kadcyla (ado-trastuzumab) may not be approved for the following: I. When Kadcyla is used in combination with other targeted biologic agents or chemotherapy agents; OR II. When the above criteria are not met and for all other indications. Coding The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member. HCPCS J9354 Injection, ado-trastuzumab emtansine, 1 mg [Kadcyla] ICD-10 Diagnosis C50.011-C50.929 Malignant neoplasm of breast C79.81 Secondary malignant neoplasm of breast D05.00-D05.92 Carcinoma in situ of breast D04.5 Z51.11 Z85.3 Carcinoma in situ of skin of breast Encounter for antineoplastic chemotherapy Personal history of malignant neoplasm of breast Document History Revised: 02/24/2023