Paclitaxel protein-bound particles (Abraxane®) is an albumin-bound form of paclitaxel with a mean particle size of approximately 130 nanometers. It is supplied as a powder, reconstituted with Sodium Chloride prior to intravenous (IV) infusion. IV infusion is given over 30 minutes every three weeks compared with three hours for Taxol® every three weeks. Pre-medication is not required with Abraxane.
All cells, whether they are healthy cells or cancer cells, go through several stages of growth. During one of the stages, the cells start to divide. Abraxane may stop the cells from dividing and growing, so they eventually die. In addition, normal cells may also be affected by Abraxane causing some of the side effects. Side effects include hair loss, infections due to low white blood cell count, neuropathy, fatigue and weakness, low red blood cell count, mouth or lip sores (mucositis), joint and muscle pain, stomach upset and diarrhea, bradycardia, low blood pressure, and/or irritation at the injection site.
Per the U.S. Food and Drug Administration (FDA) label contraindication, Abraxane therapy should not be administered to patients who have baseline neutrophil counts less than 1,500 cells/mm3. During post-marketing surveillance, rare occurrences of severe hypersensitivity reactions have been reported with Abraxane. The use of Abraxane in patients previously exhibiting hypersensitivity to paclitaxel injection or human albumin has not been studied. Patients who experience a severe hypersensitivity reaction to Abraxane should not be re-challenged with the drug.
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The medical policy is a set of guidelines supporting the current standards of practice based on available peer reviewed, evidenced based literature. The requested therapy must be proven effective for the diagnosis, procedure, drug dose, frequency and duration, if applicable, and be consistent with recommendations in at least one authoritative source. The Medical Policy is supported by the FDA approved labeling, nationally recognized societies and evidenced base guidelines. These references include, but are not limited to: Milliman, Hayes, DrugDex, NCCN, AAP, Transfusion Medicine, Biologics Compendium, Infectious Disease Society America (IDSA), American Society of Hematology, and CMS coverage policy.
Paclitaxel protein-bound particles (Abraxane®) may be considered medically necessary for the United States (U.S.) Food and Drug Administration (FDA) labeled indication of metastatic breast cancer after failure of combination chemotherapy for metastatic disease or relapse within six months of adjuvant chemotherapy. Prior therapy should have included an anthracycline, unless clinically contraindicated.
Paclitaxel protein-bound particles (Abraxane®) may be considered medically necessary for the FDA labeled indication for the treatment of 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.
Paclitaxel protein-bound particles (Abraxane®) may be considered medically necessary for the FDA labeled indication for the treatment of metastatic adenocarcinoma of the pancreas as first-line treatment, in combination with gemcitabine.
Paclitaxel protein-bound particles (Abraxane®) may be considered medically necessary for the following off-label indications:
Paclitaxel protein-bound particles (Abraxane®) for all other indications is considered experimental, investigational or unproven.
Paclitaxel protein-bound particles (Abraxane), a nanoparticle, solvent-free form of paclitaxel appears to offer several advantages compared with solvent-based paclitaxel and docetaxel. Because this new formulation does not require formulation with Cremophor EL or Tween 80, it could avoid associated hypersensitivity reactions and premedication regimes.
Breast Cancer Following Failure of Combination Chemotherapy or Relapse within Six Months of Adjuvant Therapy
A randomized, controlled, clinical trial demonstrated that treatment with paclitaxel protein-bound particles resulted in a significantly higher response rate than treatment with conventional paclitaxel in patients with metastatic breast cancer. The majority of patients had impaired performance status at baseline (64% ECOG 1 or 2), visceral metastases (79%), more than three sites of metastases (76%), received study drug as second-line or greater than second-line therapy (59%), and had prior exposure to anthracyclines (77%). Patients were randomized to receive paclitaxel protein-bound particles (260 milligrams per square meter (mg/m²) as a 30-minute intravenous infusion (n=233) or conventional paclitaxel (175 mg/m²) as a three hour intravenous infusion (n=227). Patients in the conventional paclitaxel group received standard premedication. The primary study endpoint was the reconciled target lesion response rate (TLRR), which was based on independent radiologic assessment of tumor responses reconciled with investigator responses (which included clinical information) for the first six cycles of therapy. Overall, the TLRR was 21.5% (95% confidence interval (CI), 16.19% to 26.73%) in the paclitaxel protein- bound particle group compared to 11.1% (95% CI, 6.94% to 15.09%) in the conventional paclitaxel group (p=0.003). For patients who failed combination chemotherapy or relapsed within six months of adjuvant chemotherapy, the TLRR was 15.5% (95% CI, 9.26% to 21.75%) and 8.4% (3.85% to 12.94%) for the paclitaxel protein-bound particle group (n=129) and conventional paclitaxel group (n=143), respectively.
A phase I study of intra-arterial administration of paclitaxel protein-bound particles reported a 63.6% response rate in patients with recurrent squamous cell carcinoma of the anal canal (n=12). In this dose-escalation study, protein-bound paclitaxel (dose range, 120 milligrams per square meter (mg/m²) to 300 mg/m²) was administered, without pretreatment, as a 30-minute intra-arterial infusion for a median of three cycles, with a four-week interval between cycles. The maximum tolerated dose was 270 mg/m². Eleven of 12 anal cancer patients were assessable for antitumor activity. Three patients had CR (clinical response); two pathologic and one clinical. Four patients had PR (partial response), and four had stable disease.
Head and Neck Cancer
Intra-arterial administration of paclitaxel protein-bound particles produced a 78% response rate in patients with previously untreated clinical stage T3 to T4 squamous cell carcinoma of the tongue. Of the 23 patients in the study, six patients had a tumor at the base of the tongue and 17 had a tumor of the mobile tongue. Intra-arterial treatment with paclitaxel protein-bound particles was used to induce an objective tumor response before therapy with surgery, radiation, or chemotherapy plus radiation. Patients received two to four intra-arterial infusions of paclitaxel protein-bound particles at a dose of 150 milligrams per square meter (mg/m²; n=9), 180 mg/m² (n=6), or 230 mg/m² (n=8) every three weeks. The overall response rate for the six patients who had a tumor at the base of the tongue was 83.3%; four had PR, one had a complete CR, and one had disease progression. For the 17 patients with a tumor of the mobile tongue, there were eight with PR, five with CR, three with stable disease, and one with disease progression, for an overall response rate of 76.5%. Four of the patients with CR later underwent surgery and were found to have microscopic residual disease. After a follow-up period of three to 23 months (mean 12.8 months), 17 patients had no recurrence, one patient had local recurrence six months post treatment, one patient with disease progression during intra-arterial chemotherapy who later underwent surgery had no sign of disease 11 months later. One patient with PR refused further treatment and was alive after six months of follow-up, and three patients died of disease progression to the lymph nodes 25 months, eight months and five months after treatment, respectively.
A phase I study of intra-arterial administration of paclitaxel protein-bound particles reported a 75.8% response rate (10.3% CR, 65.5% PR) in patients with head and neck squamous cell carcinoma. All 31 head and neck cancer patients had locally advanced squamous cell carcinoma with (n=14) or without (n=17) prior therapy. In this dose-escalation study, protein-bound paclitaxel (dose range, 120 milligrams per square meter (mg/m²) to 300 mg/m²) was administered, without pretreatment, as a 30-minute intra-arterial infusion for a median of three cycles, with a four-week interval between cycles. The maximum tolerated dose was 270 mg/m². Twenty-nine of 31 head and neck cancer patients were assessable for antitumor activity. Three previously untreated patients had CR (two pathologic CR and one clinical CR), 19 patients (six previously treated, 13 untreated) had PR, and four had stable disease.
Metastatic Breast Cancer, First-line Treatment as Monotherapy
A phase III, open-label, non-inferiority, and randomized clinical trial conducted in North America, the United Kingdom, and Russia/Ukraine demonstrated that treatment with single-agent paclitaxel protein-bound particles resulted in a significantly higher response rate than treatment with conventional paclitaxel as first-line therapy in patients with metastatic breast cancer. Patients (n=454) who had not previously received a taxane for metastatic disease and who had not received an adjuvant taxane within the previous year were randomized to receive paclitaxel protein-bound particles (260 milligrams per square meter (mg/m²) as a 30-minute intravenous infusion every three weeks or paclitaxel (175 mg/m²) as a three hour intravenous infusion every three weeks. Only patients in the conventional paclitaxel group received standard pre-medication. The primary endpoint was overall response rate (ORR) using RECIST (response evaluation criteria in solid tumors) criteria, with a priori subgroup analyses conducted in patients who received first-line treatment (n=186). ORR was significantly (p=0.029) improved in patients who received paclitaxel protein-bound particles (41 of 97; 42%; 95% confidence interval (CI), 32.44%-52.1%) as first-line therapy compared to those patients who received conventional paclitaxel (24 of 89; 27%; 95% CI, 17.75%-36.19%) as first-line therapy. There was a trend towards improved time to progression for patients who received paclitaxel protein-bound particles (24 weeks) compared to those who received paclitaxel (19.7 weeks) as first-line therapy, although this difference was not statistically significant. No differences in survival were found.
Treatment with paclitaxel protein-bound particles was effective in a subgroup of patients treated first-line for metastatic breast cancer in a single-arm phase II clinical trial conducted in the United States and India. All patients (n=63; median age 48.2 years; range, 28-69 years) were treated with paclitaxel protein-bound particles 300 milligrams/square meter intravenously over 30 minutes every three weeks until disease progression or unacceptable toxicity. No pre-medication or granulocyte colony-stimulating factor was administered. The primary endpoint was complete response or partial response (defined as at least a 50% reduction in tumor size). Of the 39 patients who received treatment as first-line for metastatic disease, the overall response rate was 64%.
A literature search of online and MedLine database was performed through August 2008. No additional studies were identified that would change or alter the conclusions reached above.
A search of peer-reviewed literature through November 2010 identified the following studies related to non-small cell lung cancer.
Green et al. states a multicenter phase II trial was conducted to evaluate the efficacy of Abraxane® as first line therapy in patients with confirmed non-small cell lung cancer (NSCLC). Forty three patients enrolled; overall response rate was 16%; disease control rate was 49%; median survival was 11 months; probability of surviving one year was 45%; no grade 4 treatment related toxicities occurred. The trial conclusions were: Abraxane 260mg/m² administered over 30 minutes without any pre-medication was well tolerated, and significant tumor responses and prolonged disease control were documented.
Reynolds et al. reported on an open-label, phase 2 study where 31.3% of patients with advanced non-small-cell lung cancer (NSCLC) achieved a partial response (PR) following first-line therapy with nanoparticle albumin-bound paclitaxel (nab-paclitaxel), carboplatin, and bevacizumab. Patients (n=50; median age, 67 years; range, 32 to 83 yr.) with stage IIIb or IV nonsquamous NSCLC (with evidence of inoperable local recurrence or metastases) and no history of prior chemotherapy for metastatic disease were eligible for enrollment. Previous treatment with radiotherapy was permitted. Treatment consisted of carboplatin followed by nab-paclitaxel 300 milligrams (mg)/ ² meter followed by bevacizumab 15 mg/kilogram intravenously day-one every three weeks for 4 to 6 cycles or until disease progression or therapy intolerance (median number of cycles, 4; range, 1 to 6 cycles). Response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Of 48 patients, 15 patients (31.3%; 95% confidence interval (CI), 18.1% to 44.4%) achieved a PR and 25 patients (52.1%; 95% CI, 38% to 66.2%) had stable disease (SD) (SD for six months or longer, n=11; SD for less than six months, n=14). In responding patients, the median time to response was 1.3 months (range, 1.1 to 2.5 months) and the median response duration was 9.2 months (range, 3 to 11.6 months). The median progression-free survival was 9.8 months (95% CI, 6.1 to 11.5 months) and the median overall survival (OS) was 15.8 months (95% CI, 10.4 months to not yet reached). Additionally, the 12- and 18-month OS rates were 61.2% and 36.8%, respectively.
National Comprehensive Cancer Network (NCCN) 2010-11 Guidelines
The NCCN has clinical guidelines for anal cancer, head and neck cancer, breast cancer, and non-small cell lung cancer including the use of paclitaxel protein-bound particles (Abraxane). These guidelines are dependent upon the type of cancer, clinical presentation and disease severity and/or staging.
The following is a summary of the key literature to date.
In October 2012, the FDA granted approval to Abraxane for the use of 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. The FDA approval is based on data from a randomized, multicenter, open-label study which was conducted in 1052 chemonaive patients having Stage IIIb/IV non-small cell lung cancer to compare Abraxane in combination with carboplatin to paclitaxel injection in combination with carboplatin as first–line treatment. Statistically significantly higher overall response rates were seen in the patients in the Abraxane/carboplatin arm compared to patients in the paclitaxel injection/carboplantin arm (33% versus 25%). (19)
In September 2013, the FDA granted approval to Abraxane for a new indication for use in combination with gemcitabine, as first-line treatment of patients with metastatic adenocarcinoma of the pancreas. The FDA noted that the safety and effectiveness of Abraxane was based on data from a clinical trial having 861 participants. Those treated with Abraxane and gemcitabine had a median overall survival of 1.8 months longer than those treated with gemcitabine alone (29).
The National Comprehensive Cancer Network® (NCCN)® note in Breast Cancer guidelines V 3.2012 that albumin-bound paclitaxel can be used in chemotherapy regimens, as a single agent for invasive breast cancer for recurrent or metastatic disease that is: hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative with visceral crisis, HER2-negative and either hormone receptor-negative or hormone receptor-positive and endocrine therapy refractory, or progressive with no clinical benefit after three consecutive endocrine therapy regimens or with symptomatic visceral disease. (21)
Non-Small Cell Lung Cancer
The National Comprehensive Cancer Network® (NCCN)® note in Non-Small Cell Lung Cancer guidelines V 2.2013 that albumin-bound paclitaxel can be substituted for paclitaxel or docetaxel for patients 1) who have experienced hypersensitivity reactions after receiving paclitaxel or docetaxel despite premedication or 2) in whom the standard premedications (ie, dexamethasone, H2 blockers, H1 blockers) to prevent hypersensitivity are contraindicated.(22) Rizvi, et al., in a Phase I/II study with 40 patients with stage IV non-small-cell lung cancer were treated with NAB-paclitaxel (an albumin-bound formulation of paclitaxel) without corticosteroid or antihistamine premedications. Radiologic tumor evaluation was performed every 8 weeks. The objective response rate reported was 30% (12 of 40patients; 95% Cl, 16% to 44%), median time to progression was 5 months (95% Cl, 3 to 8 months), and median overall survival was 11 months (95% Cl, 7 months to not reached). The 1-year survival was 41%. Conclusions indicated NAB-paclitaxel was well tolerated and displayed encouraging single-agent activity. No corticosteroid premedication was administered and no hypersensitivity reactions were seen. (23)
Ovarian Cancer – Epithelial Ovarian Cancer/Fallopian Tube Cancer/primary Peritoneal Cancer
The National Comprehensive Cancer Network® (NCCN)® note in Ovarian Cancer including Fallopian Tube Cancer and Primary Peritoneal Cancer V 1.2013 include Paclitaxel, albumin bound (nab-paclitaxel) as an acceptable single-agent therapy for recurrence therapy. (24) Teneriello et al., in a phase II study of nab-paclitaxel in platinum-sensitive patients with recurrent ovarian, peritoneal, or fallopian tube cancer, 44 assessable patients received nab-paclitaxel for six cycles or until disease progression. The main Inclusion criteria reported were histologically or cytologically confirmed epithelial cancer of the ovary, fallopian tube, or peritoneum (any stage, grade 2 to 3 if stage I) and measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) or elevated CA-125 (> 70 U/mL) in patients without measurable disease. The authors results noted 76% of patients had stage IIIC or IV disease, 81% had Eastern Cooperative Oncology Group performance status of 0, and 94% had prior surgery. The objective response rate (ORR) was 64% (15 complete responses [CR] and 13 partial responses [PR] among 44 assessable patients). The ORR was 64% (seven CRs and seven PRs of 22 patients), in patients meeting both RECIST and CA-125 criteria. Estimated median progression-free survival was 8.5 months. The study concluded that nab-paclitaxel is active in this group of patients with recurrent ovarian, peritoneal, or fallopian tube cancer. Toxicities were manageable. The ORR was 64%. Further studies of nab-paclitaxel in combination with platinum were warranted. (25)
The National Comprehensive Cancer Network® (NCCN) ® noted in Pancreatic Adenocarcinoma V 2.2012, acceptable chemotherapy combinations for patients with good performance status included gemcitabine and nab-paclitaxel (category 2B) in patients with locally advanced unresectable or metastatic disease. (26) Von Hoff et al., reported in a phase I/II study secreted protein acid rich in cysteine (SPARC) correlation with response to gemcitabine (G) plus nab-paclitaxel (nab-P) in patients with advanced metastatic pancreatic cancer. The authors of the study noted that pancreatic cancer cells and surrounding stroma are known to overexpress SPARC, which is associated with poor clinical outcomes. Nab-P increased tumor accumulation of paclitaxel through binding of albumin to SPARC. This study included patients with metastatic pancreatic adenocarcinoma and with no prior chemotherapy for their metastatic disease. The authors reported the following results: 63 patients received treatment. Serial PET scans of 53 patients with outside adjudication to date showed 12 (23%) complete responses, 29 (55%) partial responses (PRs) and 4 (8%) stable disease (SD). By RECIST criteria, of the 49 patients evaluable to date, 1(2%) had CR, 12 (24%) had PR, and 20 (41%) had SD. The median survival was 9 months to date. SPARC data was available for 35 patients, of which 10 (29%) were SPARC+ and 25 (71%) were SPARC-. Of these, 27 patients had evaluable response data. Patients that were SPARC+ (8/27) were more likely to be responders (6/8, 75%) than patients who were SPARC- (5/19, 26%), P = 0.03, Fisher's exact test. Median progression-free survival (PFS) increased from 4.8 months for SPARC- patients (22 pts) to 6.2 months for SPARC+ patients (9 pts); however, these data are still immature. Of 45 patients with elevated CA19–9 at baseline, 42 (93%) had maximum decrease of >40% with a median maximum decrease of 92%. Conclusions included in the study indicated SPARC+ status in these patients was associated with higher response rate and longer PFS. The combination of nab-P and G was generally well tolerated and had substantial enough antitumor activity in patients with pancreatic cancer to warrant a phase III clinical trial. (27)
National Comprehensive Cancer Network (NCCN) Guidelines
The NCCN has clinical guidelines for breast cancer, non-small cell lung cancer, ovarian cancer, and pancreatic adenocarcinoma including the use of paclitaxel protein-bound particles. These guidelines are dependent upon the type of cancer, clinical presentation and disease severity and/or staging.
Disclaimer for coding information on Medical Policies
Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.
The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.
Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.
99.25, 154.2, 154.3, 154.8, 157.0-157.9, 162.0-162.9, 174.0, 174.1, 174.2, 174.3, 174.4, 174.5, 174.6, 174.8, 174.9, 175.0, 175.9, 183.0-183.9, 195.0, 196.0, 196.1, 197.0, 198.81, 230.5, 230.6, 232.4, V10.3, V58.11
C21.0, C21.1, C21.8, C25.0-C25.9, C33, C34.00-C34.92, C50.011-C50.929, C56.1-C56.9, C57.0-C57.9, C76.0, C77.0, C77.1, C78.00-C78.02, C79.81, D01.3, D04.4, Z51.11, Z85.3, 3E04305