Subject:
Paclitaxel Protein-Bound Particles (Abraxane)
Description:
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IMPORTANT NOTE:
The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.
Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.
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Abraxane (paclitaxel protein-bound particles for injectable suspension) is a microtubule inhibitor that promotes the assembly of microtubules from tubulin dimers and stabilized microtubules by preventing depolymerization. This results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions.
On January 7, 2005, Abraxane (paclitaxel protein-bound particles for injectable suspension) received FDA approval for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy.
A multi-center trial was conducted in 460 patients with metastatic breast cancer. Patients were randomized to receive ABRAXANE at a dose of 260 mg/m2 given as a 30-minute infusion, or paclitaxel injection at 175 mg/m2 given as a 3-hour infusion. Sixty-four percent of patients had impaired performance status (ECOG 1 or 2) at study entry; 79% had visceral metastases; and 76% had > 3 sites of metastases. Fourteen percent of the patients had not received prior chemotherapy; 27% had received chemotherapy in the adjuvant setting, 40% in the metastatic setting and 19% in both metastatic and adjuvant settings. Fifty-nine percent received study drug as second or greater than second-line therapy. Seventy-seven percent of the patients had been previously exposed to anthracyclines. In this trial, patients in the ABRAXANE treatment arm had a statistically significantly higher reconciled target lesion response rate (the trial primary endpoint) of 21.5% (95% CI: 16.2% to 26.7%), compared to 11.1% (95% CI: 6.9% to 15.1%) for patients in the paclitaxel injection treatment arm.
In October 2012, paclitaxel protein-bound particles for injectable suspension) received FDA approval for locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) based on a multicenter, randomized, phase III trial. The study evaluated safety and efficacy of 100 mg/m2 30-minute infusion of albumin-bound paclitaxel and carboplatin at an area under the concentration-time curve (AUC) 6 once every 3 weeks (nab-PC) or 200 mg/m2 solvent-based paclitaxel plus carboplatin AUC 6 once every 3 weeks (sb-PC) in adult patients with stage IIIB to IV NSCLC. The study met primary endpoint with 33% overall response rate (ORR) for nab-PC as compared with 25% for sb-PC (response rate ratio, 1.313; 95% CI, 1.082 to 1.593; P=0.005).
In September 2013, paclitaxel protein-bound particles for injectable suspension) received FDA approval for first line treatment of metastatic adenocarcinoma of the pancreas in combination with gemcitabine based on a multicenter, multinational, randomized, open-label study conducted in 861 patients comparing Abraxane plus gemcitabine versus gemcitabine monotherapy. A total of 861 patients were randomized to 1:1 to Abraxane 125 mg/m2 intravenous infusion followed by gemcitabine 1000 mg/m2 intravenous infusion on days 1, 8, and 15 of each 28-day cycle. Patients randomized to gemcitabine received 1000 mg/m2 intravenous infusion weekly for 7 weeks followed by a 1-week rest period in Cycle 1 then as 1000 mg/m2 on Days 1, 8 and 15 of each subsequent 28-day cycle. Patients in both arms received treatment until disease progression or unacceptable toxicity. The major efficacy outcome measure was overall survival (OS). The overall survival was 98 patients in Abraxane and gemcitabine arm versus 71 patients in the gemcitabine arm. The median survival months was 8.5 months versus 6.7 months (P<0.0001), respectively.
The label for Abraxane was changed in September 2013 to indicate new warnings and precautions including: hematologic effects, nervous system effects, sepsis, and pneumonitis.
[INFORMATIONAL NOTE: The FDA-approved Abraxane (paclitaxel protein-bound particles for injectable suspension) package insert has the following BOXED WARNINGS:
- Abraxane for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of complications is possible only when adequate diagnostic and treatment facilities are readily available.
- Abraxane therapy should not be administered to patients with metastatic breast cancer or locally advanced or metastatic Non-Small Cell Lung Cancer who have baseline neutrophil counts of less than 1,500 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving Abraxane.
- Note: An albumin form of paclitaxel may substantially affect a drug’s functional properties relative to those of drug in solution. Do not substitute for or with other paclitaxel formulations.]
Policy:
[(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance)
The requirements of the Horizon BCBSNJ Paclitaxel Protein-Bound Particles (Abraxane) Program may require a precertification/prior authorization via MagellanRx Management. These requirements are member-specific: please verify member eligibility and requirements through the Horizon Provider Portal (www.horizonblue.com/provider). Ordering clinicians should request pre-certification from MagellanRx Management at ih.magellanrx.com or call 1-800-424-4508 (when applicable.)]
1. Abraxane (paclitaxel protein-bound particles for injectable suspension) should be administered by a healthcare professional AND the prescriber is a specialist in the area of the patient’s diagnosis (e.g. oncologist) or has consulted with a specialist in the area of the patient’s diagnosis.
2. Abraxane (paclitaxel protein-bound particles for injectable suspension) is considered medically necessary in adult patients (18 and older) for the following FDA approved indications:
- Patients with metastatic breast cancer after failure of combination chemotherapy, which included an anthracycline-unless contraindicated, for metastatic disease or relapse within 6 months of adjuvant chemotherapy who have baseline neutrophil counts of >1,500 cell/mm3
- First-line treatment in patients with locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) in combination with carboplatin, for patients who are not candidates for curative surgery or radiation therapy AND have a neutrophil count of >1,500 cells/m3
- First line treatment in patients with metastatic adenocarcinoma of the pancreas in combination with gemcitabine who have a neutrophil count of >1,500 cells/mm3
[INFORMATIONAL NOTE: As per the FDA approved package insert females of reproductive potential to use effective contraception and avoid becoming pregnant during treatment with Abraxane and for at least six months after the last dose of Abraxane. Based on findings from genetic toxicity and animal reproduction studies, advise male patients with female partners of reproductive potential to use effective contraception and avoid fathering a child during treatment with Abraxane and for at least three months after the last dose of Abraxane. ]
3. When medically necessary, Abraxane (paclitaxel protein-bound particles for injectable suspension) will be approved initially for 6 months at the following FDA-recommended doses:
- For members with metastatic or relapse breast cancer
A. Initial therapy should be started at 260 mg/m2 by intravenous infusion every 3 weeks
B. For member with severe neutropenia (neutrophils less than 500 cells/mm3 for a week or longer), or severe sensory neuropathy during Abraxane therapy, dosage should be reduced to 220mg/m2 for subsequent courses of Abraxane.
C. For recurrence of severe neutropenia or severe sensory neuropathy, additional dose reduction should be made to 180mg/m2.
D. For grade 3 sensory neuropathy, hold treatment until resolution to grade 1 or 2, followed by a dose reduction for all subsequent courses of Abraxane.
- For members with locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC)
A. Initial therapy should be started at 100 mg/m2 by intravenous infusion on Days 1, 8 and 15 of each 21 day-cycle ; administer carboplatin on Day 1 of each 21-day cycle immediately after Abraxane
- For members with adenocarcinoma of the pancreas:
A. 125 mg/m2 intravenously on days 1, 8 and 15 of each 28-day cycle; administer gemcitabine on days 1,8 and 15 of each 28-day cycle immediately after Abraxane
[INFORMATIONAL NOTE: Based on the changes made to the FDA approved package insert, the following are dosing recommendations for hepatic impairment and severe neutropenia.
· In hepatic impairment the recommended starting dose is as follows
· For patients with moderate or severe hepatic impairment, reduce the starting dose of Abraxane as shown
 | SGOT (AST) Levels | | Bilirubin Levels | Abraxane Dose MBC
(Metastatic Breast Cancer) | Abraxane Dose NSCLC
(Non-Small Cell Lung Cancer) | Abraxane Dose Pancreatic Adenocarcinoma |
| | AND | | | | |
| Moderate | <10 x ULN | 1.5 to 3.0 x ULN | 200 mg/m2
*A dose increase to 260 mg/m2 in subsequent courses should be considered if the individual tolerates the reduced dose for two cycles | 80 mg/m2
*Increase dose to100 mg/m2 in subsequent courses if the individual tolerates the reduced dose for two cycles | Not recommended |
| Severe | <10 x ULN | 3.0 to 5.0 x ULN | 200 mg/m2
*A dose increase to 260 mg/m2 in subsequent courses should be considered if the individual tolerates the reduced dose for two cycles | 80 mg/m2
*Increase dose to100 mg/m2 in subsequent courses if the individual tolerates the reduced dose for two cycles | Not recommended |
| >10 x ULN | OR | > 5.0 x ULN | Not recommended | Not recommended | Not recommended |
- Dosage recommendations are for the first course of therapy. The need for further dose adjustments in subsequent courses should be based on individual tolerance.
- Patients with bilirubin levels above the upper limit of normal were excluded from clinical trials for pancreatic or lung cancer.
[INFORMATIONAL NOTE: Based on the FDA approved package insert, the following are dosing recommendations for carboplatin AUC 6 mg•min/mL is given intravenously on Day 1 of each 21 day cycle immediately after braxane administration. Below are the FDA approved recommendations for hematologic and neurologic adverse reactions in NSCLC]
| Adverse Drug Reaction | Occurrence | Weekly Abraxane Dose (mg/m2) | Every 3-week carboplatin Dose (AUC mg•min/mL) |
Neutropienic Fever (ANC < 500/mm3 with fever >38°C)
OR
Delay of next cycle by>7 days for ANC<1500/mm3
OR
ANC<500/mm3 for >7days | First | 75 | 4.5 |
Second | 50 | 3 |
Third | Discontinue treatment |
| Platelet count <50,000/mm3 | First | 75 | 4.5 |
Second | Discontinue treatment |
| Severe sensory Neuropathy – Grade 3 or 4 | First | 75 | 4.5 |
Second | 50 | 3 |
Third | Discontinue treatment |
[INFORMATIONAL NOTE: Based on the FDA approved package insert, the following are dosing recommendations for gemcitabine: administer gemcitabine on Days 1, 8, and 15 of each 28-day cycle immediately after Abraxane. Below are the FDA approved recommendations for hematologic and neurologic adverse reactions in Adenocarcinoma of the Pancreas]
Dose Modifications for Other Adverse Drug Reactions in Patients with Adenocarcinoma of the Pancreas
| Adverse Drug Reaction | Abraxane | Gemcitabine |
Febrile Neutropenia:
Grade 3 or 4 | Withhold until fever resolves and ANC>1500; resume at next lower dose level |
Peripheral Neuropathy:
Grade 3 or 4 | Withhold until improves to <Grade 1; resume at next lower dose level | No dose reduction |
Cutaneous Toxicity:
Grade 2 or 3 | Reduce to next lower dose level; discontinue treatment if toxicity persists |
Gastrointestinal Toxicity:
Grade 3 mucositis or diarrhea | Withhold until improves to <Grade 1; resume at next lower dose level |
Dose recommendations and Modifications for Neutropenia and/or Thrombocytopenia at the Start of a Cycle or within a Cycle for Patients with Adenocarcinoma of the Pancreas
| Cycle Day | ANC (cells/mm3) | | Platelet count (cells/mm3) | ABRAXANE / Gemcitabine |
| Day 1 | < 1500 | OR | < 100,000 | Delay doses until recovery |
| Day 8 | 500 to < 1000 | OR | 50,000 to < 75,000 | Reduce 1 dose level |
| < 500 | OR | < 50,000 | Withhold doses |
| Day 15: IF Day 8 doses were reduced or given without modification: |
| 500 to < 1000 | OR | 50,000 to < 75,000 | Reduce 1 dose level from Day 8 |
| < 500 | OR | < 50,000 | Withhold doses |
| Day 15: IF Day 8 doses were withheld: |
| ≥ 1000 | OR | ≥ 75,000 | Reduce 1 dose level from Day 1 |
| 500 to < 1000 | OR | 50,000 to < 75,000 | Reduce 2 dose levels from Day 1 |
| 500 to < 1000 | OR | 50,000 to < 75,000 | Reduce 2 dose levels from Day 1 |
Abbreviations: ANC = Absolute Neutrophil Count
Dose Level Reductions for Patients with Adenocarcinoma of the Pancreas
| Dose Level | Abraxane (mg/m2) | Gemcitabine (mg/m2) |
| Full dose | 125 | 1000 |
| 1st dose reduction | 100 | 800 |
| 2nd dose reduction | 75 | 600 |
| If additional dose reduction required | Discontinue | Discontinue |
4. Medical necessity for continued therapy will be considered every 6 months if:
- Member continues to meet initial review criteria; AND
- Tumor response with stabilization of disease or decrease in size of tumor or tumor spread; AND
- Absence of unacceptable toxicity from the drug (e.g.:myelosuppression, sensory neuropathy, sepsis, pneumonitis, or severe hypersensitivity, including anaphylactic reactions)
5. Abraxane (paclitaxel protein-bound particles for injectable suspension) is considered medically necessary for off-label indications that have in effect a rating of 'Category 1' or 'Category 2A' in the current recommendations in the National Comprehensive Cancer Network (NCCN) compendium. Refer to National Comprehensive Cancer Network: Drugs and Biologics Compendium - paclitaxel, albumin bound. Available at: [https://www.nccn.org/professionals/drug_compendium/content/]
- When the patient has tried and failed generic paclitaxel, paclitaxel was not tolerated, or patient has a contraindication to paclitaxel, except for the following indications:
- Breast cancer
- Hepatobiliary cancer – Intrahepatic/Extrahepatic cholangiocarcinoma,
- Non small cell lung cancer,
- Pancreatic Adenocarcinoma
6. Other uses of Abraxane (paclitaxel protein-bound particles for injectable suspension are considered investigational including but not limited to, squamous cell carcinoma of head and neck or anal canal.
Medicare Coverage
There is no National Coverage Determination (NCD). In the absence of an NCD, coverage decisions are left to the discretion of Local Medicare Carriers. Novitas Solutions, Inc, the Local Medicare Carrier for jurisdiction JL, has not issued a determination for this service. Therefore, Medicare Advantage Products will follow the Horizon BCBSNJ Medical Policy. See generally, Local Coverage Article: Approved Drugs and Biologicals; Includes Cancer Chemotherapeutic Agents (A53049). Available at:https://www.cms.gov/medicare-coverage-database/details/article-details.aspx?articleId=53049&ver=44&name=314*1&UpdatePeriod=711&bc=AQAAEAAAAAAAAA%3d%3d&.
Medicaid Coverage
For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf
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Horizon BCBSNJ Medical Policy Development Process:
This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.
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Index:
Paclitaxel Protein-Bound Particles (Abraxane)
Abraxane (Paclitaxel Protein-Bound Particles)
References:
1. Abraxane® (paclitaxel protein-bound particles) [Prescribing information]. Abraxis BioScience, LLC. Summit, NJ. December 2019. Accessed December 2019.
2. Gradishar WJ, Krasnojon D, Cheporov S, et al. Significantly longer progression-free survival with nab-paclitaxel compared with docetaxel as first-line therapy for metastatic breast cancer. J Clin Oncol. 2009;27(22):3611-3619.
3. Green MR, Manikhas GM, Orlov S, et al. Abraxane, a novel Crenphor -free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. Ann Oncol. 2006;17(8):1263-1268
4. Rizvi NA, Riely GJ, Azzoli CG, et al. Phase I/II trial of weekly intravenous 130-nm albumin-bound paclitaxel as initial chemotherapy in patients with stage IV non-small-cell lung cancer. J Clin Oncol. 2008;26(4):639-643.
5. Damascelli B, Cantu G, Mattavelli F, et al. Intraarterial chemotherapy with polyoxyethylated castor oil free paclitaxel, incorporated in albumin nanoparticles (ABI-007): Phase II study of patients with squamous cell carcinoma of the head and neck and anal canal: preliminary evidence of clinical activity. Cancer. 2001;92(10):2592-2602
6. Damascelli B, Patelli GL, Lanocita R, et al. A novel intraarterial chemotherapy using paclitaxel in albumin nanoparticles to treat advanced squamous cell carcinoma of the tongue: preliminary findings. AJR Am J Roentgenol. 2003;181(1):253-260
7. ClinicalTrials.gov. Phase I & II Trial of Intravesicular Abraxane for Treatment-refractory Bladder Cancer. Available from: http://clinicaltrials.gov/ct2/show/NCT00583349?term=abraxane&rank=1
8. ClinicalTrials.gov. Weekly Nanoparticle Albumin-Bound Paclitaxel (Abraxane) + Weekly Cetuximab + Radiation Therapy (IMRT, Intensity-Modulated Radiation Therapy) in Patients With Stage III-IVB Head and Neck Squamous Cell Carcinoma (HNSCC). Available from: http://clinicaltrials.gov/ct2/show/NCT00736619?term=abraxane&rank=3
9. ClinicalTrials.gov. Cisplatin, temozolomide, Abraxane, with Interleukin-2 and Interferon for Metastatic Melanoma. Available from: http://clinicaltrials.gov/ct2/show/NCT00970996?term=abraxane&rank=14
10. ClinicalTrials.gov. Abraxane, gemcitabline and Xeloda for Pancreatic Adenocarcinoma. Available at: http://clinicaltrials.gov/ct2/show/NCT01161186?term=abraxane&rank=19
11. ClinicalTrials.gov. Abraxane in Front Line Therapy of Hormone Refractory Metastatic Prostate Cancer. Available at: http://clinicaltrials.gov/ct2/show/NCT00284752?term=abraxane&rank=37
12. National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. Available from: http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf Version 1.2018. Accessed 06 December 2017.
13. National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: Breast Cancer. Available from: http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Version 3.2017 Accessed 06 December 2017.
14. National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: Ovarian Cancer Including Fallopian Tube Cancer and Primary Peritoneal Cancer. Available from: http://www.nccn.org/professionals/physician_gls/PDF/ovarian.pdf. Version 4.2017. Accessed 06 Dec 2017.
15. National Comprehensive Cancer Network: Drugs and Biologics Compendium. Paclitaxel, albumin bound. 2019.http://www.nccn.org/professionals/drug_compendium/MatrixGenerator/Matrix.aspx?AID=117 [Accessed December 2019]
16. Socinski MA, Bondarenko I, Karaseva NA, et al. Weekly nab-Paclitaxel in Combination with carboplatin Versus Solvent-Based Pablitaxel Plus Carboplatin as First-Line Therapy in Patients with Advanced Non-Small Cell Lung Cancer: Final Results of a Phase III Trial. J Clin Oncol 30:2055-2062.
17. National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: Pancreatic Adenocarcinoma. Available from: https://www.nccn.org/professionals/physician_gls/pdf/pancreatic_blocks.pdf. Version 3.2017. Accessed September 2017.
18. National Comprehensive Cancer Network: Drugs and Biologics Compendium. Paclitaxel. 2019. https://www.nccn.org/professionals/drug_compendium/content/. Accessed June 2019.
Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)
CPT*
HCPCS
J9264
* CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.
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Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.
The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy
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