Commercial

Medical Policy

Notification

Paclitaxel Protein-Bound Particles for Injectable Suspension (Albumin-Bound)/(Abraxane® for Injectable Suspension)

Notification Issue Date:

This version of the policy will become effective 08/03/2020.

The medical necessity criteria have been revised to reflect the National Comprehensive Cancer Network (NCCN) compendia, including the additional indication of small bowel adenocarcinoma and the removal of genitourinary cancers.

Title:

Paclitaxel Protein-Bound Particles for Injectable Suspension (Albumin-Bound)/(Abraxane® for Injectable Suspension)

Policy #:

08.00.90p

Policy

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

This policy addresses numerous medically necessary indications* for the use of paclitaxel protein-bound particles for injectable suspension (albumin-bound) (Abraxane® for injectable suspension) in the following cancers (listed in order of appearance within the Policy section):

Ampullary Cancer	Non-Small Cell Lung Cancer
Breast Cancer Invasive/Inflammatory	Epithelial Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer//Grade 1 Endometrioid Carcinoma//Low-Grade Serous Carcinoma//Clear Cell Carcinoma of the Ovary//Mucinous Carcinoma of the Ovary//Carcinosarcoma (Malignant Mixed Müllerian Tumors)
Hepatobiliary Tract Cancers: Gallbladder Cancer//Biliary Tract Cancers: Intrahepatic Cholangiocarcinoma/Extrahepatic Cholangiocarcinoma	Pancreatic Adenocarcinoma
Kaposi Sarcoma	Small Bowel Adenocarcinoma
Melanoma: Cutaneous/Uveal	Endometrial Carcinoma

MEDICALLY NECESSARY

Paclitaxel protein-bound particles for injectable suspension (albumin-bound) (Abraxane® for injectable suspension) are considered medically necessary and, therefore, covered for any of the following indications:

AMPULLARY ADENOCARCINOMA

Subsequent therapy for disease progression in individuals with good performance status (PS) (Eastern Cooperative Oncology Group [ECOG] 0-1, with good biliary drainage and adequate nutritional intake) and pancreatobiliary and mixed type if previously treated with fluoropyrimidine-based therapy in combination with gemcitabine
Subsequent therapy for disease progression in select individuals (poor PS and ECOG PS 2) with pancreatobiliary and mixed type in combination with gemcitabine
First-line therapy in combination with gemcitabine for pancreatobiliary and mixed-type disease for the following indications:

Unresectable localized

Stage IV resected ampullary cancer

Metastatic disease at initial presentation

for individuals with good PS and ECOG 0-1, with good biliary drainage and adequate nutritional intake^*
for individuals with poor PS and ECOG PS 2

Neoadjuvant therapy, with or without subsequent chemoradiation, in combination with gemcitabine for pancreatobiliary and mixed-type localized disease, in high-risk individuals (i.e., imaging findings, markedly elevated CA 19-9, markedly elevated carcinoembryonic antigen [CEA], large primary tumors, large regional lymph nodes, excessive weight loss, extreme pain)

*may be followed by chemoradiation for palliative indications (NCCN recommended)

BREAST CANCER, INVASIVE
NOTE: The medical necessity of this drug is based on meeting the requirements of the human epidermal growth factor 2 (HER2) testing, as well as the medical necessity criteria below:

Single-agent or in combination with carboplatin for the treatment of individuals with high tumor burden, rapidly progressing disease, and visceral crisis for individuals with no response to preoperative systemic therapy, or recurrent unresectable (local or regional) or stage IV (M1) HER2-negative disease that is:
- Hormone receptor-negative
- Hormone receptor-positive with a visceral crisis or endocrine therapy refractory
In combination with pembrolizumab for PD-L1 positive triple-negative recurrent unresectable (local or regional) or stage IV (M1) disease:

As NCCN-preferred first line of therapy
As second and subsequent lines of therapy if PD-L1 inhibitor has not been previously used

As a third-line therapy and beyond in combination with trastuzumab (Herceptin®) for HER2-positive disease recurrent unresectable (local or regional) or stage IV (M1) disease that is:
- Hormone receptor-negative
- Hormone receptor-positive with or without endocrine therapy refractory
As a substitute for paclitaxel (i.e., Taxol®, Onxol®) or docetaxel (i.e., Taxotere) for individuals with hypersensitivity reactions

BREAST CANCER, INFLAMMATORY

Single-agent or in combination with carboplatin for the treatment of individuals with high tumor burden, rapidly progressing disease, and visceral crisis in individuals with no response to preoperative systemic therapy, or for recurrent unresectable (local or regional) or stage IV (M1) HER2-negative disease that is:
- Hormone receptor-negative
- Hormone receptor-positive with a visceral crisis or endocrine therapy refractory

As a third-line therapy and beyond in combination with trastuzumab (Herceptin®) for HER2-positive disease individuals with no response to preoperative systemic therapy, or for recurrent unresectable (local or regional) or stage IV (M1) disease that is:
- Hormone receptor-negative
- Hormone receptor-positive with or without endocrine therapy refractory

In combination with pembrolizumab for PD-L1 positive triple-negative disease individuals with no response to preoperative systemic therapy, or recurrent unresectable (local or regional) or stage IV (M1) disease:

As NCCN preferred first line of therapy
As second and subsequent lines of therapy if PD-L1 inhibitor has not been previously used

As a substitute for paclitaxel (i.e., Taxol®, Onxol®) or docetaxel (i.e., Taxotere) for hypersensitivity reactions

BREAST CANCER, METASTATIC

Treatment of metastatic breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior chemotherapy must have included an anthracycline unless clinically contraindicated.

HEPATOBILIARY CANCERS

In combination with gemcitabine as primary treatment for unresectable or metastatic intrahepatic or extrahepatic cholangiocarcinoma
In combination with gemcitabine as subsequent therapy for the treatment of progression on or after systemic therapy in individuals with unresectable or metastatic intrahepatic or extrahepatic cholangiocarcinoma

GALLBLADDER CANCER

The primary treatment for unresectable or metastatic disease in combination with gemcitabine
Subsequent treatment for progression on or after systemic treatment for unresectable or metastatic disease in combination with gemcitabine

KAPOSI SARCOMA

Subsequent systemic therapy, given alone (no HIV) or with antiretroviral therapy (ART) for individuals with HIV (PWH), for relapsed/refractory advanced cutaneous, oral, visceral, or nodal disease that has progressed on or not responded to first-line systemic therapy, and progressed on alternate first-line systemic therapy

NOTE: includes classic Kaposi, posttransplant, and iatrogenic variant of Kaposi sarcoma.

no HIV = HIV negative. PWH = HIV positive

MELANOMA, CUTANEOUS
Single-agent therapy or in combination with carboplatin for metastatic or unresectable disease as second-line or subsequent therapy for disease progression or after maximum clinical benefit from BRAF targeted therapy

MELANOMA, UVEAL
Single-agent therapy for distant metastatic disease

NON-SMALL-CELL LUNG CANCER (NSCLC)

For the treatment of individuals who are not candidates for curative surgery or radiation as first-line therapy for locally advanced or metastatic non-small-cell lung cancer (NSCLC), in combination with carboplatin
For the treatment of recurrent, advanced, or metastatic disease as first-line therapy for PD-L1 expression-positive (≥1%) tumors that are negative for actionable molecular markers* and no contraindications** to PD-1 or PD-L1 inhibitors, and PS 0-2 in combination with pembrolizumab and carboplatin for squamous cell histology (excluding locoregional recurrence or symptomatic local disease [except for mediastinal lymph node recurrence with prior radiation therapy] with no evidence of disseminated disease) (NCCN preferred regimen) or in combination with carboplatin and atezolizumab for nonsquamous cell histology
For the treatment of recurrent, advanced, or metastatic disease as a single agent for individuals with ECOG PS 2, or in combination with carboplatin for PS 0-2 if contraindications** to the addition of PD-1 or PD-L1 inhibitors (e.g., pembrolizumab or atezolizumab) and PS 0-1 for both nonsquamous cell histology and squamous cell histology, or other recommended regimen for nonsquamous cell histology and PS 2, or preferred for squamous cell histology and PS 2 (excluding locoregional recurrence or symptomatic local disease [except for mediastinal lymph node recurrence with prior radiation therapy] with no evidence of disseminated disease) as:

Initial systemic therapy for negative actionable molecular markers* and PD-L1 expression positive <1% with contraindications to PD-1 or PD-L1 inhibitors
Initial systemic therapy for PD-L1 <1% and negative for actionable molecular biomarkers*
First-line therapy for EGFR exon 20 mutation-positive tumors
First-line therapy for KRAS G12C mutation-positive tumors
First-line or subsequent therapy for BRAF V600E-mutation-positive tumors
First-line or subsequent therapy for NTRK 1/2/3 gene fusion-positive tumors
First-line or subsequent therapy for MET exon 14 skipping mutation-positive tumors
First-line or subsequent therapy for RET rearrangement-positive tumors
Subsequent therapy for sensitizing EGFR mutation-positive (e.g., exon 19 deletion or L858R) tumors and prior erlotinib +/- (ramucirumab or bevacizumab), afatinib, gefitinib, osimertinib, or dacomitinib therapy
Subsequent therapy for EGFR S768I, L861Q, and/or G719X mutation-positive tumors and prior afatinib, osimertinib, erlotinib, gefitinib, or dacomitinib therapy
Subsequent therapy for ALK rearrangement-positive tumors and prior crizotinib, certinib, alectinib, or brigatinib therapy
Subsequent therapy for ROS1 rearrangement-positive tumors and prior crizotinib, entrectinib, or ceritinib therapy
Subsequent therapy for PD-L1 expression-positive (≥1%) tumors and negative for actionable molecular markers* and no prior platinum-containing chemotherapy after prior PD-1/PD-L1 inhibitor

Treatment for recurrent, advanced, or metastatic disease for individuas with PS 0-1 and no contraindications** to PD-1 or PD-L1 inhibitors, in combination with pembrolizumab and carboplatin for squamous cell histology (NCCN preferred regimen) or in combination with carboplatin and atezolizumab for nonsquamous cell histology (excluding locoregional recurrence or symptomatic local disease [except for mediastinal lymph node recurrence with prior radiation therapy] with no evidence of disseminated disease) as:

Initial systemic therapy for PD-L1 <1% and negative for actionable molecular markers*
First-line therapy for EGFR exon 20 mutation-positive tumors
First-line therapy for KRAS G12C mutation-positive tumors
First-line or subsequent therapy for RET rearrangement-positive tumors
Subsequent therapy for EGFR S768I, L861Q, and/or G719X mutation-positive tumors and prior afatinib, osimertinib, erlotinib, gefitinib, or dacomitinib therapy
First-line (useful in certain circumstances) or subsequent therapy for BRAF V600E-mutation positive tumors
First-line (useful in certain circumstances) or subsequent therapy for NTRK1/2/3 gene fusion-positive tumors
First-line (useful in certain circumstances) or subsequent therapy for MET exon 14 skipping mutation-positive tumors
Subsequent therapy for ROS1 rearrangement-positive tumors and prior crizotinib, entrectinib, or ceritinib therapy

As subsequent systemic therapy as a single agent (if not already given) for recurrent, advanced, or metastatic disease in individuals with PS 0-2
As a substitute for either paclitaxel or docetaxel in individuals who have experienced hypersensitivity reactions after receiving paclitaxel or docetaxel despite premedication, or for individuals in whom standard hypersensitivity premedications are contraindicated

*If there is insufficient tissue to allow testing for all of EGFR, ALK, ROS1, BRAF, NTRK1/2/3, MET, and RET, repeat biopsy and/or plasma testing should be done. If these are not feasible, treatment is guided by available results and, if unknown, these individuals are treated as though they do not have driver oncogenes

**Contraindications for treatment with PD-1/PD-L1 inhibitors may include active or previously documented autoimmune disease and/or current use of immunosuppressive agents, or presence of an oncogene (e.g., EGFR [exon 19 deletions, p.L858R point mutation in exon 21], ALK rearrangements, RET rearrangements), which would predict lack of benefit

OVARIAN CANCER / FALLOPIAN TUBE CANCER / PRIMARY PERITONEAL CANCER

Epithelial Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer

Carcinosarcoma (Malignant Mixed Müllerian Tumors)

Clear Cell Carcinoma of the Ovary

Mucinous Carcinoma of the Ovary

Peritoneal Cancer - Grade 1 Endometrioid Carcinoma

Therapy for persistent disease or recurrence in combination with carboplatin if platinum-sensitive persistent disease or recurrence for individuals with confirmed taxane hypersensitivity in individuals with complete remission and relapse within 6 months after completing prior chemotherapy

As a single-agent therapy for persistent disease or recurrence (excluding immediate treatment for biochemical relapse)
- For progression on primary, maintenance, or recurrence therapy (platinum-resistant disease)
- For stable or persistent disease (if not on maintenance therapy) (platinum-resistant disease)
- For complete remission and relapse 6 months after completing chemotherapy (platinum-resistant disease)
- For radiographic and/or clinical relapse in individuals with previous complete remission and relapse, within 6 months, after completing prior chemotherapy (platinum-sensitive disease)
May be a substitute for paclitaxel in individuals who experience a hypersensitivity reaction to paclitaxel

Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer - Low-Grade Serous Carcinoma

Useful in certain circumstances in combination with carboplatin if platinum-sensitive recurrence for individuals with confirmed taxane hypersensitivity
May be a substitute for paclitaxel in individuals who experience a hypersensitivity reaction to paclitaxel
Single-agent therapy for platinum-sensitive or platinum-resistant recurrence

PANCREATIC ADENOCARCINOMA

First-line therapy, or as continuation (maintenance) therapy if no disease progression (after at least 4-6 months of chemotherapy, assuming acceptable tolerance) after first-line therapy in individuals with metastatic disease and good PS in combination with either of the following or both of the following:
- Gemcitabine (preferred) if ECOG PS 0-2
- Gemcitabine and cisplatin if ECOG PS 0-1
First-line chemotherapy, or induction therapy followed by chemoradiation in selected individuals, without systemic metastases, or as continuation (subsequent) therapy if no disease progression after first-line therapy for individuals with locally advanced disease and good PS (ECOG PS 0-2) in combination with gemcitabine (NCCN-preferred regimen)
Neoadjuvant treatment (NCCN-preferred regimen) in combination with gemcitabine, with or without subsequent chemoradiation for one of the following:

Resectable disease in high-risk individuals (i.e., very highly elevated CA 19-9, large primary tumors, large regional lymph nodes, excessive weight loss, extreme pain)
Biopsy-positive borderline resectable disease

As NCCN-preferred first-line therapy for metastatic disease in individuals with good PS (ECOG PS 0-2), in combination with gemcitabine
Subsequent treatment in combination with gemcitabine for locally advanced or metastatic disease for individuals with good PS (ECOG PS 0-2) and disease progression who were previously treated with fluoropyrimidine-based therapy
Therapy in individuals with good PS if < 6 months from completion of primary therapy and previously treated with fluoropyrimidine-based therapy in combination with gemcitabine if ECOG PS 0-2 with or without chemoradiation for local recurrence in the pancreatic operative bed after resection for recurrent metastatic disease with or without local recurrence after resection
Therapy in individuals with good PS if ≥ 6 months from completion of primary therapy in combination with gemcitabine*** if ECOG PS 0-2 with* or without chemoradiation for local recurrence in the pancreatic operative bed after resection for recurrent metastatic disease with or without local recurrence after resection

*If not previously done

**As repeat systemic therapy previously administered

***As alternate systemic therapy not previously used

SMALL BOWEL ADENOCARCINOMA

As a single agent or in combination with gemcitabine for advanced or metastatic small bowel adenocarcinoma in individuals with prior oxaliplatin exposure in the adjuvant setting or contraindication

As initial therapy
As subsequent therapy in individuals who previously received initial therapy with nivolumab with or without ipilimumab, or pembrolizumab, or dostarlimab-gxly

Subsequent therapy as a single agent or in combination with gemcitabine for advanced or metastatic small bowel adenocarcinoma in individuals who are appropriate or not appropriate for intensive therapy

UTERINE NEOPLASMS

Single-agent therapy for endometrial carcinoma:
- For disease suitable for primary surgery as additional treatment with vaginal brachytherapy for stage IA disease (NCCN-preferred regimen)
- For disease suitable for primary surgery as additional treatment with or without sequential external beam radiation therapy (EBRT) and with or without vaginal brachytherapy for stage IB-IV disease
- For disease not suitable for primary surgery as primary treatment with or without sequential EBRT and with or without brachytherapy

As a single-agent primary treatment of endometrial carcinoma (except for chemotherapy alone for disease not suitable for primary surgery in individuals with suspected or gross cervical involvement):
Single-agent therapy for the treatment of recurrent or metastatic disease:

For disseminated metastases
With sequential EBRT and with or without brachytherapy for locoregional recurrence in individuals with no prior radiotherapy to the site of recurrence, or previous brachytherapy only
After surgical exploration, with sequential EBRT for locoregional recurrence in individuals with disease confined to the vagina or paravaginal soft tissue, or in pelvic, para-aortic, or common iliac lymph nodes
After surgical exploration, with or without sequential EBRT for locoregional recurrence in individuals with upper abdominal or peritoneal disease
With or without sequential palliative EBRT or brachytherapy for locoregional recurrence in individuals who have received prior EBRT to the site of recurrence

Single-agent therapy for the treatment of metastatic endometrial carcinoma:

For disease that is suitable for primary surgery as additional treatment with or without sequential EBRT with or without vaginal brachytherapy after total hysterectomy/bilateral salpingo-oophorectomy (TH/BSO) that is not suitable for primary surgery as primary treatment with or without sequential EBRT and with or without brachytherapy

Adjuvant treatment for surgically staged individuals as a single agent with or without EBRT and with or without vaginal brachytherapy for stage III-IV disease

EXPERIMENTAL/INVESTIGATIONAL

All other uses for paclitaxel protein-bound particles for injectable suspension (albumin-bound) (Abraxane® for injectable suspension) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

MANDATES

PENNSYLVANIA MEMBERS

In accordance with the Commonwealth of Pennsylvania's Act 6 of 2020 or Fair Access to Cancer Treatment Act, for members who are enrolled in Pennsylvania commercial products who have stage 4, advanced metastatic cancer, refer to the Medical Policy titled "Coverage of Anticancer Prescription Oral and Injectable Drugs and Biologics and Supportive Agents" (08.01.08) for additional information regarding the applicable coverage of drugs and biologics.

Guidelines

BLACK BOX WARNINGS

Refer to the specific manufacturer's prescribing information for any applicable Black Box Warnings.

HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 (HER2) PROTEIN OVEREXPRESSION TESTING

Paclitaxel protein-bound particles for injectable suspension (albumin-bound) (Abraxane® for injectable suspension) is considered medically necessary and, therefore, covered for the indication(s) identified above for individuals who meet the applicable criteria, and whose results have been verified by one of the following US Food and Drug Administration (FDA) approved diagnostic tests:

Immunohistochemical (IHC) assay with a result of 0 or 1+
Fluorescence in situ hybridization (FISH) test (ratio less than 1.8)
Single-probe in situ hybridization (ISH) test with average HER2 copy number less than 4.0 signals/cell
Dual-probe ISH test HER2/CEP17 (chromosome enumeration probe 17) ratio less than 2.0 AND average HER2 copy number less than 4.0 signals/cell

Confirmatory tests should be performed for borderline results as follows:

If IHC assay has a result of 2+, confirm with ISH test of the same sample or a new test with IHC or ISH (if new sample available).
If FISH test has a HER2 gene/chromosome 17 ratio of 1.8-2.0, confirm with FISH re-test; additional cell counting and recalculation of the ratio; or IHC assay.
If single-probe ISH assay has an average HER2 copy number result of 4.0 to less than 6.0 signals/cell, confirm with dual-probe ISH or with IHC (if same sample), or with a new ISH or IHC (if new sample available).
If dual-probe ISH assay has a HER2/CEP17 ratio less than 2.0 and an average HER2 copy number result of 4.0 to less than 6.0 signals/cell, confirm with one of the following: IHC (if same sample), alternative ISH chromosome 17 probe, or order a new test with ISH or IHC (if new sample available).

THE EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) PERFORMANCE STATUS

The ECOG Performance Status was originally published in 1982 in the American Journal of Clinical Oncology*. ECOG states: "These scales and criteria are used by doctors and researchers to assess how an individual's disease is progressing, assess how the disease affects the daily living abilities of the individual, and determine appropriate treatment and prognosis. They are included here for health care professionals to access."

KARNOFSKY PERFORMANCE STATUS

The Karnofsky Performance Status is a method to assess the ability of an individual with cancer to perform ordinary tasks. This method is used to score functional impairment, compare the effectiveness of therapies, and assess the prognosis of a patient. The Karnofsky index ranges between 100 and 0.

Karnofsky Performance Status	ECOG Performance Status
100- Normal; no evidence of disease	0- Fully active, able to carry on all pre-disease performance without restriction
90- Minor signs or symptoms of the disease 80- Normal activity with effort; some signs or symptoms	1- Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work
70- Cares for self; unable to carry on normal activity 60- Occasional assistance required; capable of most self-care	2- Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50 percent of waking hours
50- Requires assistance, frequent medical care 40- Disabled; requires special care/assistance	3- Capable of only limited self-care, confined to bed or chair more than 50 percent of waking hours
30- Severely disabled; hospitalization indicated 20- Hospitalization necessary; requires active supportive care 10- Moribund; progressing rapidly	4- Completely disabled. Cannot carry on any self-care: totally confined to bed or chair
0- Dead	5- Dead

*Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol.1982;5(6):649-655.

*Karnofsky DA, Burchenal JH. The clinical evaluation of chemotherapeutic agents in cancer. In: Macleod CM, ed. Evaluation of Chemotherapeutic Agents in Cancer. New York: Columbia University Press; 1949:191-205.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, paclitaxel protein-bound particles for injectable suspension (albumin-bound) (Abraxane® for injectable suspension) are covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Paclitaxel protein-bound particles for injectable suspension (albumin-bound) (Abraxane® for injectable suspension) was approved by the FDA on January 7, 2005, for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy.

On October 11, 2012, the FDA granted paclitaxel protein-bound particles for injectable suspension (albumin-bound) (Abraxane® for injectable suspension), a supplemental approval for use in combination with carboplatin for the initial treatment of individuals with locally advanced or metastatic non-small-cell lung cancer who are not candidates for curative surgery or radiation therapy.

On September 6, 2013, the FDA approved paclitaxel protein-bound particles for injectable suspension (albumin-bound) (Abraxane® for injectable suspension), a supplemental approval for use in combination with gemcitabine for the first-line treatment of adults with metastatic adenocarcinoma of the pancreas.

PEDIATRIC USE

The safety and effectiveness of paclitaxel protein-bound particles for injectable suspension (albumin-bound) (Abraxane® for injectable suspension) in the pediatric population have not been evaluated.

Description

Paclitaxel protein-bound particles for injectable suspension (albumin-bound) (Abraxane® for injectable suspension) is an antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. Abraxane® is an albumin-bound form of paclitaxel, a natural product with antitumor activity. In contrast to solvent-based paclitaxel, which requires premedication to decrease the risks of hypersensitivity reactions (e.g., difficulty breathing, hives, swollen eyes and lips), Abraxane® requires no premedication.

Paclitaxel protein-bound particles for injectable suspension (albumin-bound) (Abraxane® for injectable suspension) was approved by the US Food and Drug Administration (FDA) on January 7, 2005, for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or after relapse within 6 months of adjuvant chemotherapy. Per the FDA label, prior therapy should include an anthracycline unless clinically contraindicated.

The FDA approval was based on a randomized, comparative, multicenter study of 460 individuals that compared standard paclitaxel with premedication to Abraxane® without premedication in individuals with metastatic breast cancer. Individuals on the Abraxane® treatment had a statistically significantly higher reconciled target lesion response rate of 21.5% compared to 11.1% for individuals on the standard paclitaxel therapy. There was no significant difference in overall survival between the two groups.

On October 11, 2012, the FDA approved paclitaxel protein-bound particles for injectable suspension (albumin-bound) (Abraxane® for injectable suspension) for use in combination with carboplatin for the initial treatment of individuals with locally advanced or metastatic non-small-cell lung cancer who are not candidates for curative surgery or radiation therapy. The FDA approval was based on a multicenter, randomized, open-label study that was conducted comparing Abraxane® in combination with carboplatin to paclitaxel injection in combination with carboplatin as first-line treatment in 1,052 chemo-naive individuals with advanced non-small-cell lung cancer. Paclitaxel injection was administered as an intravenous infusion following premedication. In both treatment arms, carboplatin was administered intravenously on Day 1 of each 21-day cycle after completion of Abraxane®/paclitaxel infusion. Treatment was administered until disease progression or development of an unacceptable toxicity. Individuals in the Abraxane®/carboplatin arm had a statistically significantly higher overall response rate compared with individuals in the paclitaxel injection/carboplatin arm (33% vs 25%). There was no statistically significant difference in overall survival between the two study arms.

On September 6, 2013, the FDA approved paclitaxel protein-bound particles for injectable suspension (albumin-bound) (Abraxane® for injectable suspension) as first-line treatment for use to treat individuals with metastatic adenocarcinoma of the pancreas in combination with gemcitabine. The FDA approval was based on a multicenter, multinational, open-label study, conducted in individuals with metastatic adenocarcinoma of the pancreas (n=861). Abraxane® in combination with gemcitabine were compared with gemcitabine monotherapy as first-line treatment. Individuals in the Abraxane®/gemcitabine arm, on average, lived 1.8 months longer than those in the gemcitabine-monotherapy arm. Additionally, individuals in the Abraxane®/gemcitabine arm also experienced longer median progression-free survival (delay in tumor growth) than those in the gemcitabine monotherapy arm (5.5 months vs 3.7 months).

DIAGNOSTIC TESTS FOR HER2 PROTEIN OVEREXPRESSION

HER2 protein overexpression is detected either by immunohistochemical (IHC) assay or with a type of in situ hybridization (ISH) test for gene amplification (e.g., fluorescence in situ hybridization [FISH], chromogenic in situ hybridization [CISH], dual in situ hybridization [DISH]. Each technique has its own advantages and disadvantages, such as accuracy of results, timeliness of results, and whether the sample will fade over time. The FDA has approved several commercially available tests to aid in the selection of breast cancer patients for Abraxane® therapy. The NCCN and American Society of Clinical Oncology (ASCO) guidelines further recommend that IHC assay and ISH testing should only be done at laboratories that are accredited to perform HER2 testing.

An IHC test result is reported as 0 or 1+ (negative), 2+ (borderline), or 3+ (positive).
A FISH test result is reported as a HER2 gene/chromosome 17 ratio less than 1.8 (negative), a ratio of 1.8 to less than 2.0 (borderline), or a ratio of 2.0 or greater (positive).
A single-probe ISH test result is reported as: average HER2 copy number less than 4.0 signals/cell (negative); 4.0 to less than 6.0 signals/cell (borderline); 6.0 or greater signals/cell (positive).
A dual-probe ISH test result is reported as HER2/CEP17 (chromosome enumeration probe 17) ratio 2.0 or greater (positive); HER2/CEP17 ratio less than 2.0 AND average HER2 copy number less than 4.0 signals/cell (negative); HER2/CEP17 ratio less than 2.0 AND average HER2 copy number 4.0 to less than 6.0 signals/cell (borderline); HER2/CEP17 ratio less than 2.0 AND average HER2 copy number 6.0 signals/cell or greater (positive).

The NCCN and ASCO both have issued guidelines for HER2 testing in invasive breast cancer that call for confirming a borderline or equivocal result:

IHC assay result of 2+: confirm with ISH test (if same sample), or with a new IHC or ISH test (if new sample available).
FISH assay: confirm with either a repeat FISH test or an additional cell counting and recalculation of the ratio. If a repeat FISH test remains equivocal, then an IHC assay is recommended for confirmation.
Single-probe ISH assay: confirm with dual-probe ISH or with IHC (if same sample), or with a new ISH or IHC (if new sample available).
Dual-probe ISH assay: confirm with one of the following: IHC (if same sample), alternative ISH chromosome 17 probe, or order a new test with ISH or IHC (if new sample available).

OFF-LABEL INDICATIONS

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.

References

Abraxane for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound). [prescribing information]. Summit, NJ: Celgene Corporation: August 2020. Available at: https://www.abraxane.com/. Accessed July 15, 2022.

American Hospital Formulary Service (AHFS). Drug Info 2022. Abraxane. [Lexi-Comp website]. 03/28/2022. Available at: http://online.lexi.com/lco/action/home# [via subscription only]. Accessed July 15, 2022.

Elsevier Gold's Standard Clinical Pharmacology Compendium. Nanoparticle Albumin-Bound Paclitaxel. [ClinicalKey Web site]. 03/22/2021. Available at: https://www.clinicalkey.com/pharmacology/ [via subscription only]. Accessed July 15, 2022.

Giordano SH, Temin S, Kirshner JJ, et al. Systemic therapy for patients with advanced human epidermal growth factor receptor 2-positive breast cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2014;May 5.

Gradishar W, Tjulandin S, Davidson N, et al. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol. 2002;23(31):7794-7803.

Hammond MEH, Hayes DF, Dowsett M, et al. ASCO-CAP guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010;28(16):2784-2795.

Harris L, Fritsche H, Mennel R, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007; 25(33):5287-5312.

Hersh Evan M, O'Day SJ, Ribas A, et al. A phase 2 clinical trial of nab–paclitaxel in previously treated and chemotherapy–naive patients with metastatic melanoma. Cancer. 2010;116(1):155-63.

Karnofsky DA, Burchenal JH. The clinical evaluation of chemotherapeutic agents in cancer. In: Macleod CM, ed. Evaluation of Chemotherapeutic Agents in Cancer. New York: Columbia University Press; 1949:191-205.

Kottschade LA, Suman VJ, Amatruda T III, et al. A phase II trial of nab–paclitaxel (ABI–007) and carboplatin in patients with unresectable stage IV melanoma. Cancer. 2011;117(8):1704-10.

Lexi-Drugs Compendium. Abraxane. 07/07/2022. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed July 15, 2022.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Ampullary Adenocarcinoma.V1.2022. [NCCN Web site]. 03/09/2022. Available at: http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed July 15, 2022.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Breast cancer.V4.2022. [NCCN Web site]. 06/21/2022. Available at: http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed July 15, 2022.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Kaposi Sarcoma. V1.2022. [NCCN Web site]. 02/03/2022. Available at: https://www.nccn.org/professionals/physician_gls/pdf/kaposi.pdf. Accessed July 15, 2022.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Melanoma: Cutaneous V2.2021. [NCCN Web site]. 02/19/2021. Available at: https://www.nccn.org/professionals/physician_gls/pdf/cutaneous_melanoma.pdf. Accessed July 15, 2022.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Melanoma: Uveal  V2.2022. [NCCN Web site]. 04/05/2022. Available at: https://www.nccn.org/professionals/physician_gls/pdf/cutaneous_melanoma.pdf. Accessed July 15, 2022.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Melanoma: cutaneous V3.2022. [NCCN Web site]. 04/11/2022. Available at: https://www.nccn.org/professionals/physician_gls/pdf/cutaneous_melanoma.pdf. Accessed July 15, 2022.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Hepatobiliary Cancers. V2.2022. [NCCN Web site]. 07/15/2022. Available at: https://www.nccn.org/professionals/physician_gls/pdf/hepatobiliary.pdf. Accessed July 15, 2022.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Non-small cell lung cancer. V3.2022. [NCCN Web site]. 03/16/2022. Available at: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed July 15, 2022.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Ovarian Cancer. V3.2022. [NCCN Web site]. 07/25/2022. Available at: http://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf. Accessed July 26, 2022.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Pancreatic adenocarcinoma. V1.2022. [NCCN Web site]. 02/24/2022. Available at: http://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf. Accessed July 15, 2022.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Small bowel adenocarcinoma. V1.2022. [NCCN Web site]. 03/09/2022. Available at: http://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf. Accessed July 15, 2022.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Uterine Neoplasms. V1.2022. [NCCN Web site]. 11/04/2021. Available at: https://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf. Accessed July 15, 2022.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium. Paclitaxel, albumin bound. [NCCN Web site]. Available at: https://www.nccn.org/professionals/drug_compendium/content/ [via subscription only]. Accessed July 15, 2022.

Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol.1982;5(6):649-655.

Truven Health Analytics. Micromedex® DrugDex® Compendium. Paclitaxel protein-bound. 04/27/2022. Greenwood Village, CO. [Micromedex® Solutions Web site]. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed July 15, 2022.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs@FDA. Drug details: Abraxane for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound). [FDA Web site]. Original: 01/07/05. (Revised: 08/25/20). Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed July 15, 2022.

Wolff AC, Hammond MEH, Allison KH, et al. Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol. (2018) 36:2105-22.

Coding

CPT Procedure Code Number(s)

N/A

ICD - 10 Procedure Code Number(s)

N/A

ICD - 10 Diagnosis Code Number(s)

See Attachment A.

HCPCS Level II Code Number(s)

J9258 Injection, paclitaxel protein-bound particles (teva) not therapeutically equivalent to j9264, 1 mg

J9259 Injection, paclitaxel protein-bound particles (american regent) not therapeutically equivalent to j9264, 1 mg

J9264 Injection, paclitaxel protein-bound particles, 1 mg

Revenue Code Number(s)

N/A

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History

Revisions From 08.00.90p:

01/02/2024

This policy has been identified for the HCPCS code update, effective 01/02/2024.

The following HCPCS code has been added to this policy:

J9258 Injection, paclitaxel protein-bound particles (teva) not therapeutically equivalent to j9264, 1 mg

Revisions From 08.00.90o:

07/01/2023

This policy has been identified for the HCPCS code update, effective 07/01/2023.

The following HCPCS code has been added to this policy:

J9259 Injection, paclitaxel protein-bound particles (american regent) not therapeutically equivalent to J9264, 1 mg

Revisions From 08.00.90n:

08/29/2022

This version of the policy will become effective 08/29/2022.

The medical necessity criteria have been revised to reflect the National Comprehensive Cancer Network (NCCN) compendia, including the additional indication of ampulary adenocarcinoma and the removal of peritoneal cancer - low-grade serous carcinoma/ovarian borderline epithelial tumors (Low Malignant Potential) with invasive implants.

The following policy criteria were revised, per NCCN:

Policy Section:

NSCLC
Ovarian cancer
Pancreatic cancer
Small bowel adenocarcinoma
Uterine neoplasms

The following ICD-10 codes were added to the policy:
C17.3 Meckel's diverticulum, malignant
C23 Malignant neoplasm of gallbladder
C24.1 Malignant neoplasm of ampulla of Vater
C79.81 Secondary malignant neoplasm of breast

D03.51 Melanoma in situ of anal skin

D03.52 Melanoma in situ of breast (skin) (soft tissue)

C25.4 Malignant neoplasm of endocrine pancreas

10/01/2021

This policy has been identified for the ICD-10 code update, effective 10/01/2021.

The following ICD-10 code has been added to attachment A:

C56.3 Malignant neoplasm of bilateral ovaries

Revisions From 08.00.90m:

12/20/2021

This version of the policy will become effective 12/20/2021.

The medical necessity criteria have been revised to reflect the National Comprehensive Cancer Network (NCCN) compendia, including the additional indication of small bowel adenocarcinoma and the removal of genitourinary cancers.

The following policy criteria were revised, per NCCN:

Policy Section:

Breast Cancer, Invasive
Kaposi sarcoma
Melanoma
NSCLC
Pancreatic cancer
Small bowel adenocarcinoma
Ovarian cancer
Hepatobiliary cancers
Uveal melanoma
Uterine neoplasms

The following ICD-10 codes were added to the policy:
C17.3 Meckel's diverticulum, malignant
C23 Malignant neoplasm of gallbladder

Revisions From 08.00.90l:

10/01/2021

This policy has been identified for the ICD-10 code update, effective 10/01/2021.

The following ICD-10 code has been added to attachment A:

C56.3 Malignant neoplasm of bilateral ovaries

Revisions From 08.00.90k:

08/03/2020

Revisions From 08.00.90j:

08/26/2019

This policy has undergone a routine review and the medical necessity criteria have been revised to reflect the National Comprehensive Cancer Network (NCCN) compendia, including the additional indication of intrahepatic and extrahepatic cholangiocarcinoma.

Revisions From 08.00.90i:

12/31/2018

This policy has been updated to be consistent with the US Food and Drug Administration (FDA) labeling and NCCN compendia, including the additional indication of Kaposi sarcoma.

Revisions From 08.00.90h:

10/01/2018

This policy has been identified for the ICD-10 CM code update, effective 10/01/2018.

The following CD-10 CM codes have been termed from this policy:
C43.11 Malignant melanoma of right eyelid, including canthus
C43.12 Malignant melanoma of left eyelid, including canthus

The following ICD-10 CM codes have been added to to the attachment A:
C43.111 Malignant melanoma of right upper eyelid, including canthus
C43.112 Malignant melanoma of right lower eyelid, including canthus
C43.121 Malignant melanoma of left upper eyelid, including canthus
C43.122 Malignant melanoma of left lower eyelid, including canthus

Revisions From 08.00.90g:

12/27/2017

This version of the policy will become effective 12/27/2017.

This policy has been updated to be consistent with the US Food and Drug Administration (FDA) labeling and NCCN compendia.

Policy criteria was updated to include new recommendations from NCCN:

Criteria were updated for Primary Cancers of the Urinary tract
Criteria were updated for Invasive Breast Cancer
Criteria were updated for Non-Small Cell Lung Cancer
Criteria were updated for Ovarian Cancer
Criteria were updated for Pancreatic Adenocarcinoma
Criteria were updated for Melanoma
Uterine neoplasm was added as a new indication

Description of Karnofsky Performance Scores added.

The following codes were added: C54.0, C54.1, C54.2, C54.3, C54.8, C54.9, C55, C57.9.

The following codes were removed: C45.1, Z17.0, Z17.1.

Effective 10/05/2017 this policy has been updated to the new policy template format.

Version Effective Date:

1/1/2024

Version Issued Date:

1/2/2024

Version Reissued Date: