Coverage Policy Manual
Policy #: 2017012
Category: Pharmacy
Initiated: April 2017
Last Review: April 2018
  Nab-Paclitaxel (Abraxane™)

Description:
Paclitaxel protein-bound particles, also known as “nanoparticle albumin-bound” (nab)-paclitaxel, are microtubule inhibitors that result in the assembly and stabilization of microtubules by preventing depolymerization.  This stability results in the inhibition of interphase and mitotic cellular functions, preventing cell division.  (Clinical Pharmacology, 2017).  
 
Regulatory Status
In January 2005, Abraxane™ for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) was approved for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated.  In October 2012, the FDA approved Abraxane™ for locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC), as first-line treatment in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy.  In September 2013, the FDA approved Abraxane™ for a new indication for the first-line treatment of patients with metastatic adenocarcinoma of the pancreas, in combination with gemcitabine (U.S. Food and Drug Administration 2005, 2012, 2013).

Policy/
Coverage:
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage
Criteria
 
Nab-paclitaxel meets primary coverage criteria in the treatment of the following listed indications:
 
(FDA labeled)
 
    1. Metastatic breast cancer, after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated.
    2. Locally advanced or metastatic non-small cell lung cancer (NSCLC), as first-line treatment in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy.
    3. Metastatic adenocarcinoma of the pancreas as first-line treatment, in combination with gemcitabine.
 
 
Off-label (2017)
 
    1. Bladder Cancer
      • Used as a single agent for clinical stage T4b or T2-4a, N1-3 disease, or for recurrence post cystectomy, or for metastatic disease as subsequent systemic therapy as an alternate regimen
2. Bladder Cancer - Primary Carcinoma of the Urethra
      • Used as a single agent as subsequent systemic therapy for recurrent or metastatic disease
3. Upper GU Tract Tumors
      • Used as a single agent as subsequent systemic therapy for metastatic disease as an alternate regimen
4. Urothelial Carcinoma of the Prostate
      • Used as a single agent as subsequent systemic therapy for metastatic disease as an alternate regimen
5. Metastatic Breast cancer
      • Therapy in combination with trastuzumab for human epidermal growth factor receptor 2-positive recurrent or metastatic trastuzumab-exposed disease
          • with symptomatic visceral disease or visceral crisis
          • that is hormone receptor-negative or hormone receptor-positive and endocrine therapy refractory
6. Cervical Cancer
      • Second-line therapy as a single agent for either local/regional recurrence or distant metastases
7. Melanoma
      • Single-agent therapy for metastatic or unresectable disease as second-line or subsequent therapy for disease progression or after maximum clinical benefit from BRAF targeted therapy for patients with performance status 0-2
8. Non-Small Cell Lung Cancer (NSCLC)
      • Treatment for recurrence or metastasis as a single agent for patients with performance status (PS) 2 or in combination with carboplatin for (PS) 0-2 as
      • subsequent therapy for sensitizing EGFR mutation-positive tumors and prior erlotinib, afatinib, gefitinib, or osimertinib therapy
      • subsequent therapy for ALK rearrangement-positive tumors and prior crizotinib, ceritinib, or alectinib therapy
      • subsequent therapy for ROS1 rearrangement-positive tumors and prior crizotinib therapy
      • subsequent therapy for PD-L1 expression-positive (≥50%) and EGFR, ALK, and ROS1 negative tumors and prior pembrolizumab therapy
9. Epithelial Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer
      • Single-agent therapy for persistent disease or recurrence
 
 
 
Dosing:
The prescribed regimen must be in compliance with FDA-approved dosing, with a dosing regimen of less than 260mg/m2 every 3 weeks.
 
Nab-paclitaxel is given as an IV infusion over 30 minutes.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary
Coverage Criteria
The use of Nab-paclitaxel for the treatment of any other indications or any other circumstances than those outlined above does not meet member benefit certificate primary coverage criteria.
 
For members with contracts without primary coverage criteria, the use of Nab-paclitaxel for the treatment of any other indications or any other circumstances than those outlined above is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Rationale:
The safety and efficacy of nab-paclitaxel (ABI-007) was evaluated in a multicenter phase II clinical trial in which 63 women with histologically confirmed and measurable metastatic breast cancer (MBC) were treated with nab-paclitaxel by IV infusion.  48 patients had received prior chemotherapy, and 39 patients had not received prior treatment. Overall response rates (complete or partial responses) were 48% for all patients. For patients who received nab-paclitaxel as first-line and greater than first-line therapy for their metastatic disease, the respective response rates were 64% and 21%. Median time to disease progression was 26.6 weeks, and median survival was 63.6 weeks. No severe hypersensitivity reactions were reported. Toxicities observed were typical of paclitaxel and included neutropenia (24%), sensory neuropathy (11%), and febrile neutropenia (5%). Patients received a median of six treatment cycles.  The authors concluded that treatment with nab-paclitaxel resulted in significant antitumor activity in patients with MBC, including those receiving the drug as first-line therapy (Ibrahim et al, 2005).  
 
The safety and efficacy of nab-paclitaxel (ABI-007) was evaluated also evaluated in a comparative phase III trial in which 454 patients with metastatic breast cancer (MBC) were treated with either nab-paclitaxel or standard paclitaxel.  ABI-007 demonstrated significantly higher response rates compared with standard paclitaxel (33% v 19%, respectively) and significantly longer time to tumor progression (23.0 v 16.9 weeks, respectively). The incidence of grade 4 neutropenia was significantly lower for nab-paclitaxel compared with standard paclitaxel (9% v 22%, respectively) despite a 49% higher paclitaxel dose. Grade 3 sensory neuropathy was more common in the nab-paclitaxel arm than in the standard paclitaxel arm (10% v 2%, respectively). No hypersensitivity reactions occurred with ABI-007 despite the absence of premedication and shorter administration time. The authors concluded that nab-paclitaxel demonstrated greater efficacy and a favorable safety profile compared with standard paclitaxel in patients with MBC (Gradishar et al, 2005).  
 
The safety and efficacy of nab-paclitaxel plus carboplatin in advanced NSCLC was evaluated in a phase III clinical trial in which 1052 untreated patients with phase III to IV NSCLC were randomly assigned to received either nab-paclitaxel  plus carboplatin or solvent-based paclitaxel plus carboplatin.  Nab-paclitaxel was as effective as sb-paclitaxel.  PFS was 6.3 months for the nab-paclitaxel group, as compared to the sb-paclitaxel group at 5.8 months.  Overall survival was 12.1 in the nab-paclitaxel group versus 11.2 months in the sb-paclitaxel group.  Safety was demonstrated in that significantly less neuropathy, neutropenia , arthralgia and myalgia occurred in the nab-paclitaxel groups.  However, less thrombocytopenia and anemia occurred in the sb-paclitaxel groups.  (Socinski, 2012)
 
The efficacy of nab-paclitaxel in recurrent ovarian, peritoneal and Fallopian tube was evaluated by two studies.  The first was a phase II clinical trial in which 47 patients with histologically or cytologically confirmed epithelial cancer of the ovary, Fallopian tube, or peritoneum received nab-paclitaxel 260mg/m2 every 21 days for 6 cycles or until disease progression. The ORR was 64% (15 complete responses and 13 partial responses).  Estimated median progression-free survival (PFS) was 8.5 months.  (Teneriello, 2009).  The second study evaluating nab-paclitaxel included 47 patients with platinum- and -taxane resistant cancer defined by persistence or progression after primary chemotherapy or recurrence within 6 months of completing treatment.  The median progression-free survival (PFS) was 4.5 months. Overall survival was 17.4 months.  (Coleman, 2011)
 
Nab-paclitaxel was evaluated for the treatment of recurrent or persistent advanced cervical cancer in a Phase II trial in which 37 patients were enrolled, and 35 were eligible.  Of the 35 patients, 10 had a partial response and 25 had stable disease.  Median PFS was 5 months and median overall survival was 9.4 months.  Adverse events included neutropenia in 2 patients, which resolved with dose reduction and grade III neurotoxicity in 1 patient which resolved upon discontinuation. (Alberts, 2012)
 
Treatment options for urothelial cancer are limited, with typical responses less than 20% and without survival benefit. Nab-paclitaxel was studied for metastatic urothelial carcinoma in an open-label single group multicenter study.  Patients were at least 18 years old with histologically-confirmed  locally advanced or metastatic urothelial cancer.  Treatment continued until disease progression or occurrence of unacceptable toxic effects.  The primary end-point was objective tumor response, defined by a CR or PR according to Response Evaluation Criteria in Solid Tumors criteria.  The study enrolled 48 patients; 1 had a complete response and 12 had a partial response for an ORR of 27.7%. (Ko, 2013)
 
Nab-paclitaxel was evaluated in histologically or cytologically confirmed metastatic melanoma in a cohort study that included 37 chemotherapy-naïve patients and 37 previously treated patients.   The median progression-free survival (PFS) was 3.5 months for previously treated and 4.5 months for chemotherapy-naïve patients, and the median survival was 12.1 months and 9.6 months, respectively. The probability of being alive and free of disease progression at 6 months was 27% for the previously treated cohort and 34% for the chemotherapy-naive cohort; the probability of surviving 1 year was 49% and 41%, respectively, for the previously treated and chemotherapy-naive cohorts. Authors noted that this response rate, PFS, and survival compare favorably to current standard therapy. (Hersh, 2010)   Another study of nab-paclitaxel in metastatic melanoma enrolled 76 patients in a phase II trial in which patients with unresectable stage IV melanoma received nab-paclitaxel and carboplatin.  Of the patients enrolled, 41 where chemotherapy-naïve and 35 had received prior treatment.  There were 10 responses in the chemotherapy naïve cohort (25.6%) and 3 responses in the prior treatment cohort (8.8%).  Median progression-free survival was 4.5 months in the CN cohort and 4.1 months in the PT cohort. Median overall survival (OS) was 11.1 months in the CN group and 10.9 months in the PT group.  (Kottschade, 2011)
 
Nab-paclitaxel was evaluated for use in the treatment of invasive bladder cancer in a phase-1 study which enrolled 18 patients with recurrent, high grade (Ta, T1 and Tis) transitional cell carcinoma of the bladder for which at least 1 prior standard intravesical regimen failed.  Of the 18 patients 5 (28%) had no evidence of disease at posttreatment evaluation (McKiernan et al, 2011).  

CPT/HCPCS:
J9264Injection, paclitaxel protein-bound particles, 1 mg

References: Alberts DS, Blessing JA, Landrum LM, et al.(2012) Phase II trial of nab-paclitaxel in the treatment of recurrent or persistent advanced cervix cancer: A gynecologic oncology group study. Gynecologic oncology. 2012;127(3):451-455. doi:10.1016/j.ygyno.2012.09.008.

Celgene Corporation.(2015) Abraxane® [package insert]. Summit, NJ: Celgene Corporation.; 2015

Clinical Pharmacology [Internet].(2017) Nanoparticle Albumin-Bound Paclitaxel. Tampa (FL): Elsevier. c2017- [cited 2017 March 14]. Available from: http://www.clinicalpharmacology.com

Gradishar WJ, Tjulandin S, Davidson N, Shaw H, Desai N, Bhar P, Hawkins M, and O'Shaughnessy J.(2005) Phase III Trial of Nanoparticle Albumin-Bound Paclitaxel Compared With Polyethylated Castor Oil–Based Paclitaxel in Women With Breast Cancer. Journal of Clinical Oncology 2005 23:31, 7794-7803

Hersh, E. M., O'Day, S. J., Ribas, A., Samlowski, W. E., Gordon, M. S., Shechter, D. E., Clawson, A. A. and Gonzalez, R.(2010) A phase 2 clinical trial of nab-paclitaxel in previously treated and chemotherapy-naive patients with metastatic melanoma. Cancer, 2010.116: 155–163. doi:10.1002/cncr.24720

Ibrahim NK, Samuels B, Page R, Doval D, Patel KM, Rao SC, Nair MK, Bhar P, Desai N, and Hortobagyi GN.(2005) Multicenter Phase II Trial of ABI-007, an Albumin-Bound Paclitaxel, in Women With Metastatic Breast Cancer. Journal of Clinical Oncology 2005 23:25, 6019-6026

Ko YJ, Canil CM, Mukherjee SD, et al.(2013) Nanoparticle albumin-bound paclitaxel for second-line treatment of metastatic urothelial carcinoma: A single group, multicentre, phase 2 study. Lancet Oncol. 2013;14(8):769-776.

Kottschade LA, Suman VJ, Amatruda T 3rd, et al.(2011) A phase II trial of nab-paclitaxel (ABI-007) and carboplatin in patients with unresectable stage IV melanoma : A North Central Cancer Treatment Group Study, N057E(1). Cancer. 2011;117(8):1704-1710.

McKiernan JM, Barlow LJ, Laudano MA, et al.(2011) A phase I trial of intravesical nanoparticle albumin-bound paclitaxel in the treatment of bacillus Calmette-Guérin refractory nonmuscle invasive bladder cancer. J Urol. 2011;186(2):448-451.

NCCN(2017) NCCN Compendia. https://www.nccn.org/professionals/drug_compendium/MatrixGenerator/Matrix.aspx?AID=5. Accessed March 14, 2017.

Socinski MA, Bondarenko I, Karaseva NA, et al.(2012) Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel 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. 2012;30(17):2055-2062.


Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
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