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 #:

08.00.90u

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	Melanoma: Cutaneous/Uveal
Breast Cancer Invasive/Inflammatory	Non-Small Cell Lung Cancer
Biliary Tract Cancers: Gallbladder Cancer/Intrahepatic Cholangiocarcinoma/Extrahepatic Cholangiocarcinoma	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)
Cervical cancer	Pancreatic Adenocarcinoma
Endometrial Carcinoma	Small Bowel Adenocarcinoma
Kaposi Sarcoma	Vaginal Cancer

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 as 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:

for individuals with good poor performance status (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 if ECOG performance status 0–2 for pancreatobiliary and mixed-type localized disease, in high-risk individuals (i.e., equivocal or indeterminate imaging findings, markedly elevated CA 19-9, markedly elevated carcinoembryonic antigen (CEA), large primary tumors, large regional lymph nodes, excessive weight loss, extreme pain)

(National Comprehensive Cancer Network [NCCN] note: *May be followed by chemoradiation for palliative indications .

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 for recurrent unresectable (local or regional) or stage IV (M1) HER2-negative disease that is hormone receptor–positive with a visceral crisis or endocrine therapy refractory as one of the following:
- First-line therapy (chemotherapy preferred) if no germline BRCA 1/2 mutation and/or HER2 IHC 0+, 1+, or 2+/ISH negative
- Second-line therapy if not a candidate for fam-trastuzumab deruxtecan-nxki
- Third-line therapy and beyond
Single-agent therapy or in combination with carboplatin (in select individuals with high tumor burden, rapidly progressing disease, and visceral crisis) for recurrent unresectable (local or regional) or stage IV (M1) triple-negative breast cancer (TNBC) as one of the following:
In combination with pembrolizumab for PD-L1 positive (PD-L1 CPS ≥10) triple-negative recurrent unresectable (local or regional) or stage IV (M1) disease:

As NCCN-preferred first-line therapy

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

As a forth 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 taxanes (paclitaxel or docetaxel ) 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–positive with a visceral crisis or endocrine therapy refractory for any line of therapy:

First-line therapy if no germline BRCA 1/2 mutation

Second-line therapy if not a candidate for fam-trastuzumab deruxtecan-nxki

Third-line therapy and beyond

Single-agent therapy or in combination with carboplatin (in select 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) triple-negative breast cancer (TNBC) as one of the following:

First-line therapy if PD-L1 CPS <10 and no germline BRCA 1/2 mutation

Second-line therapy

Third-line therapy and beyond

Fourth-line therapy and beyond in combination with trastuzumab for HER2-positive disease in individuals with no response to preoperative systemic therapy, or recurrent unresectable (local or regional) or stage IV (M1) disease that is one of the following:

Hormone receptor–negative

Hormone receptor–positive with or without endocrine therapy

In combination with pembrolizumab for PD-L1 (PD-L1 CPS ≥10) positive triple-negative disease for 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-1/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 six months of adjuvant chemotherapy. Prior chemotherapy must have included an anthracycline unless clinically contraindicated.

CERVICAL CANCER

Second-line or subsequent therapy as a single agent for any of the following:

Local/regional recurrence
Stage IVB or recurrence with distant metastases
Persistent, recurrent, or metastatic small cell neuroendocrine carcinoma of the cervix (NECC)

BILIARY CANCERS

Intrahepatic Cholangiocarcinoma, Extrahepatic Cholangiocarcinoma

In combination with gemcitabine as primary treatment for unresectable or resected gross residual (R2), or metastatic disease

In combination with gemcitabine as subsequent therapy for the treatment of progression on or after systemic therapy in individuals with unresectable or resected gross residual (R2), or metastatic disease

Gallbladder Cancer

As neoadjuvant systemic therapy in combination with gemcitabine for resectable locoregionally advanced disease that presents as one of the following:

Incidental finding of suspicious mass during surgery where hepatobiliary surgery expertise unavailable
Incidental finding on pathologic review (cystic duct node–positive)
Mass on imaging

As primary treatment for unresectable or resected gross residual (R2) disease, or metastatic disease in combination with gemcitabine

Subsequent treatment for progression on or after systemic treatment for unresectable or resected gross residual (R2) disease, or metastatic disease in combination with gemcitabine

KAPOSI SARCOMA

Subsequent systemic therapy for individuals intolerant to paclitaxel, 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 disease as second-line or subsequent therapy for metastatic or unresectable disease if not eligible for any of the recommended immunotherapy or targeted therapy options (due to progression on prior therapy, unacceptable toxicity, or comorbidities)

MELANOMA, UVEAL
As single-agent therapy for distant metastatic or unresectable disease.

NON-SMALL CELL LUNG CANCER (NSCLC)

Treatment for recurrent, advanced, or metastatic disease as first-line therapy for PD-L1 expression–positive (≥1%) tumors that are negative for actionable molecular biomarkers* (may be KRAS G12C mutation–positive) and no contraindications** to PD-1 or PD-L1 inhibitors and PS 0-2 (excluding locoregional recurrence or symptomatic local disease [except for mediastinal lymph node recurrence with prior radiation therapy] with no evidence of disseminated disease, or for PD-L1 ≥50% as one of the following:

In combination with pembrolizumab and carboplatin for squamous cell histology (NCCN preferred)
In combination with carboplatin and atezolizumab for nonsquamous cell histology
In combination with tremelimumab-actl, durvalumab, and carboplatin

Treatment for recurrent, advanced, or metastatic disease (except for locoregional recurrence or symptomatic local disease [excluding progression after subsequent systemic therapy and for locoregional recurrence or symptomatic local disease (excluding mediastinal lymph node recurrence with prior radiation therapy) with no evidence of disseminated disease]

As treatment for recurrent, advanced, or metastatic disease for those with performance status 0-2 if contraindications** to PD-1 or PD-L1 inhibitors or if EGFR exon 19 deletion or L858R; ALK, RET, or ROS1 rearrangements for both nonsquamous cell histology and squamous cell histology (except for locoregional recurrence or symptomatic local disease (excluding mediastinal lymph node recurrence with prior radiation therapy) with no evidence of disseminated disease) for any of the following:

In combination with carboplatin

As a single agent

The above regimens are used as one of the following:

initial systemic therapy for PD-L1 expression positive (≥1%) and negative for actionable molecular biomarkers* (may be KRAS G12C mutation positive) with contraindications to PD-1 or PD-L1 inhibitors

initial systemic therapy for PD-L1 <1% and negative for actionable molecular biomarkers* (may be KRAS G12C mutation positive)

first-line therapy for EGFR exon 20 insertion mutation positive tumors

first-line or subsequent therapy for BRAF V600E mutation positive tumors

first-line or subsequent therapy for NTRK1/2/3 gene fusion positive tumors

first-line or subsequent therapy for MET exon 14 skipping mutation positive tumors

subsequent therapy for RET rearrangement positive tumors and prior pralsetinib, selpercatinib, or cabozantinib

first-line therapy for ERBB2 (HER2) mutation positive tumors

first-line therapy for NRG1 gene fusion positive tumors

subsequent therapy for EGFR exon 19 deletion or exon 21 L858R tumors and prior erlotinib +/- (ramucirumab or bevacizumab), afatinib, gefitinib, osimertinib, amivantamab-vmjw + lazertinib, 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 alectinib, brigatinib, ceritinib, crizotinib, ensartinib, or lorlatinib therapy

subsequent therapy for ROS1 rearrangement positive tumors and prior crizotinib, entrectinib, repotrectinib, or lorlatinib therapy

subsequent therapy for PD-L1 expression positive (≥1%) tumors and negative for actionable molecular biomarkers* after prior PD-1/PD-L1 inhibitor but no prior platinum-containing chemotherapy

Treatment for recurrent, advanced, or metastatic disease for induviduals with performance status (PS) 0-2 and no contraindications** to PD-1 or PD-L1 inhibitors and no EGFR exon 19 deletion or L858R; ALK, RET, or ROS1 rearrangements, in combination with any of the following:

Atezolizumab and carboplatin for nonsquamous cell histology [except for locoregional recurrence or symptomatic local disease (excluding mediastinal lymph node recurrence with prior radiation therapy) with no evidence of disseminated disease]

Carboplatin and pembrolizumab for squamous cell histology (preferred)

Tremelimumab-actl, durvalumab, and carboplatin

The above regimens are used as one of the following:

initial systemic therapy for PD-L1 <1% and negative for actionable molecular biomarkers* (may be KRAS G12C mutation positive)

first-line therapy for EGFR exon 20 insertion mutation positive tumors

first-line or subsequent therapy for BRAF V600E mutation positive tumors

first-line or subsequent therapy for NTRK1/2/3 gene fusion positive tumors

first-line or subsequent therapy for MET exon 14 skipping mutation positive tumors

first-line therapy for ERBB2 (HER2) mutation positive tumors

first-line therapy for NRG1 gene fusion positive tumors

subsequent therapy for EGFR S768I, L861Q, and/or G719X mutation positive tumors and prior afatinib, osimertinib, erlotinib, gefitinib, or dacomitinib therapy

Single agent (if not already given) as subsequent systemic therapy for recurrent, advanced or metastatic disease in those with performance status 0-2
For the treatment of individuals who are not candidates for curative surgery or radiation as first-line therapy for locally advanced or metastatic NSCLC, in combination with carboplatin.
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

*Complete genotyping for EGFR, KRAS, ALK, ROS1, BRAF, NTRK1/2/3, MET, RET, and ERBB2 (HER2), via biopsy and/or plasma testing. If a clinically actionable marker is found, it is reasonable to start therapy based on the identified marker. 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

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 six 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 prior to six months after completing chemotherapy (platinum-resistant disease)

For radiographic and/or clinical relapse in individuals with previous complete remission and relapse, within six months, after completing prior chemotherapy (platinum-sensitive disease)

May be a substitute for paclitaxel in individuals who experience a hypersensitivity reaction to paclitaxel

In combination with carboplatin if persistent disease or recurrence for induviduals with confirmed taxane hypersensitivity for any of the following:

For progression on primary, maintenance, or recurrence therapy (platinum-resistant)*

For stable or persistent disease (if not on maintenance therapy) (platinum-resistant)*

For complete remission and relapse prior to six months after completing chemotherapy (platinum-resistant)*

For induviduals with complete remission and relapse within six months after completing prior chemotherapy (platinum-sensitive)

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

In combination with carboplatin if platinum-sensitive or platinum-resistant* 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

*Platinum agents have limited activity when the disease has demonstrated growth through a platinum-based regimen, and platinum rechallenge is generally not recommended in this setting

PANCREATIC ADENOCARCINOMA

As first-line treatment of individualss with metastatic adenocarcinoma of the pancreas, in combination with gemcitabine

First-line chemotherapy, or induction therapy followed by chemoradiation in selected individuals, without systemic metastases, for individuals with locally advanced disease and good PS (ECOG PS 0-1) with good biliary drainage and adequate nutritional intake) 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 or as induction therapy followed by chemoradiation in individuals without systemic metastases for locally advanced disease and intermediate PS (ECOG PS 2) 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 0-1, with good biliary drainage and adequate nutritional intake) and disease progression who were previously treated with fluoropyrimidine-based therapy in combination with gemcitabine
Therapy in individuals with good PS if less than six 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 if six or more months from completion of primary therapy in combination with gemcitabine*/**/*** (NCCN preferred if ECOG PS 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 if less than six months from completion of primary therapy and previously treated with fluoropyrimidine-based therapy in combination with gemcitabine**/*** (NCCN preferred if ECOG PS 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

First-line therapy for metastatic disease with good PS (defined as ECOG PS 0-1, with good biliary drainage and adequate nutritional intake) in combination with any of the following:

Gemcitabine (preferred regimen)

Gemcitabine and cisplatin

First-line therapy for metastatic disease with intermediate PS (ECOG PS 2) in combination with gemcitabine (preferred regimen)
Subsequent therapy for locally advanced or metastatic disease and disease progression if intermediate PS (ECOG PS 2) and previously treated with fluoropyrimidine-based therapy in combination with gemcitabine

NCCN notes: *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 for one of the following:

As initial therapy if an individual has received previous FOLFOX/CAPEOX in the adjuvant setting within the past 12 months or is contraindicated
As second-line and subsequent therapy (if not previously given)

UTERINE NEOPLASMS

Single-agent as second-line or subsequent therapy for the treatment of recurrent disease (if not previously used) for any of the following:

For isolated metastases

For disseminated metastases with or without sequential palliative external beam radiation therapy (EBRT)

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, or 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

VAGINAL CANCER

Second-line or subsequent therapy as a single agent for one of the following:

Local/regional recurrence
Stage IVB or recurrent distant metastases

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.

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.

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.

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.

MANDATES

The laws of the state where the benefit contract is issued determine the mandated coverage.

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: October 2022. Available at: https://www.abraxane.com/. Accessed May 1, 2024.

American Hospital Formulary Service (AHFS). Drug Info 5/21/2025. Abraxane. [Lexi-Comp website]. 04/18/2024. Available at: http://online.lexi.com/lco/action/home# [via subscription only]. Accessed May 1, 2024.

Elsevier Gold's Standard Clinical Pharmacology Compendium. Nanoparticle Albumin-Bound Paclitaxel. [ClinicalKey Web site]. 05/15/2025. Available at: https://www.clinicalkey.com/pharmacology/ [via subscription only]. Accessed May 1, 2024.

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. 05/27/2025. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed May 1, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Ampullary Adenocarcinoma.V2.2025. [NCCN Web site]. 01/10/2025. Available at: ampullary.pdf (nccn.org). Accessed May 1, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Breast cancer.V4.2025. [NCCN Web site]. 04/17/2025. Available at: http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed May 1, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Cervical cancer.V4.2025. [NCCN Web site]. 03/24/2025. Available at: http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed May 1, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Kaposi Sarcoma. V2.2025. [NCCN Web site]. 01/14/2025. 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 V2.2025. [NCCN Web site]. 01/28/2025. Available at: https://www.nccn.org/professionals/physician_gls/pdf/cutaneous_melanoma.pdf. Accessed May 1, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Melanoma: Uveal V1.2025.. [NCCN Web site]. 02/11/2025. Available at:uveal.pdf (nccn.org). Accessed May 1, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Biliary Cancers. V1.2025. [NCCN Web site].03/20/2025. Available at: btc.pdf (nccn.org). Accessed May 1, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Non-small cell lung cancer. V4.2025. [NCCN Web site]. 05/23/2025. Available at: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed May 1, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Ovarian Cancer. V2.2025. [NCCN Web site]. 05/23/2025. Available at: http://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf. Accessed May 1, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Pancreatic adenocarcinoma. V2.2025. [NCCN Web site]. 02/03/2025. Available at: http://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf. Accessed May 1, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Small bowel adenocarcinoma. V3.2024. [NCCN Web site]. 04/30/2024. Available at: small_bowel.pdf (nccn.org). Accessed May 1, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Uterine Neoplasms. V3.2025. [NCCN Web site]. 03/07/2025. Available at: https://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf. Accessed May 1, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Vaginal Cancer. V5.2025. [NCCN Web site]. 02/28/2025. Available at: https://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf. Accessed May 1, 2024.

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 May 1, 2024.

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. 02/28/2024. Greenwood Village, CO. [Micromedex® Solutions Web site]. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed May 1, 2024.

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 May 1, 2024.

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)

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 08.00.90u

10/01/2025

This policy has been identified for the ICD-10 CM code update, effective 10/01/2025.

The following ICD-10 CM codes have been added to this policy:

C50.A0 Malignant inflammatory neoplasm of unspecified breast
C50.A01 Malignant inflammatory neoplasm of right breast
C50.A02 Malignant inflammatory neoplasm of left breast

Revisions From 08.00.90t:

07/28/2025

This version of the policy will become effective 07/28/2025

The medical necessity criteria have been revised to reflect the National Comprehensive Cancer Network (NCCN) compendia, including the additional indication of cervical cancer and vaginal cancer

The following policy criteria were revised, per NCCN:

Policy Section:

Ampullary Cancer
Breast Cancer
Kaposhi sarcoma
Melanoma
Non-small cell lung cancer
Ovarian cancer
Pancreatic cancer
Uterine neoplasms

The following ICD-10 code was added to the policy as medically necessary:
C44.89 Other specified malignant neoplasm of overlapping sites of skin

Revisions From 08.00.90s:

01/01/2025

This policy has been identified for the HCPCS code update, effective 01/01/2025.
Inclusion of a policy in a Code Update memo does not imply that a full review of
the policy was completed at this time.

The following HCPCS code has been removed from this policy:

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

Revisions From 08.00.90r:

10/01/2024

This policy has been identified for the HCPCS code update, effective 10/01/2024.

The following HCPCS code has been removed from this policy:

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

Revisions From 08.00.90q:

06/17/2024

This version of the policy will become effective 06/17/2024.

The medical necessity criteria have been revised to reflect the National Comprehensive Cancer Network (NCCN) compendia, including the additional indication of cervical cancer and vaginal cancer

The following policy criteria were revised, per NCCN:

Policy Section:

Ampullary Cancer
Breast Cancer
Melanoma
Non-small cell lung cancer
Ovarian cancer
Pancreatic cancer
Small bowel adenocarcinoma
Uterine neoplasms

The following policy criteria were added, per NCCN

Cervical cancer
Vaginal Cancer

The following ICD-10 codes were added to the policy:

C52 Malignant neoplasm of vagina
C53.0 Malignant neoplasm of endocervix
C53.1 Malignant neoplasm of exocervix
C53.8 Malignant neoplasm of overlapping sites of cervix uteri
C53.9 Malignant neoplasm of cervix uteri, unspecified

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 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:

10/1/2025

Version Issued Date:

10/1/2025

Version Reissued Date:

Commercial

Medical Policy

Notification

Policy

Guidelines

Description

References

Coding

CPT Procedure Code Number(s)

ICD - 10 Procedure Code Number(s)

ICD - 10 Diagnosis Code Number(s)

HCPCS Level II Code Number(s)

Revenue Code Number(s)

MPMiscCodesNarrativesPub​

Coding and Billing Requirements

Cross Reference

Policy History

MPMiscCodesNarrativesPub