Clinical UM Guideline

 

Subject: Paclitaxel, protein-bound (Abraxane®)
Guideline #:  CG-DRUG-50 Publish Date:    05/10/2018
Status: Revised Last Review Date:    05/03/2018

Description

This document addresses the indications for protein-bound paclitaxel (Abraxane, Abraxis BioScience, LLC., Celgene Corp, Summit, NJ) a microtubule inhibitor agent approved by the U.S. Food and Drug Administration (FDA) to treat relapsed or metastatic breast cancer, locally advanced or metastatic non-small cell lung cancer, metastatic adenocarcinoma of the pancreas, and other off-label oncologic conditions.

Clinical Indications

Medically Necessary:

  1. Breast Cancer
    1. Protein-bound paclitaxel is considered medically necessary in the treatment of relapsed or metastatic breast cancer when the following criteria are met:
      1. Used as a single agent; and
      2. Used in a single line of therapy; or
    2. Protein-bound paclitaxel is considered medically necessary in the treatment of any breast cancer in an individual with confirmed taxane (that is, solvent-based paclitaxel or docetaxel) hypersensitivity.
       
  2. Malignant Melanoma

    Protein-bound paclitaxel is considered medically necessary in the treatment of relapsed or refractory melanoma when the following criteria are met:
    1. Used as a single agent; and
    2. Individual has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 following at least one prior therapy.
       
  3. Non-Small Cell Lung Cancer (NSCLC)
    1. Protein-bound paclitaxel is considered medically necessary in the treatment of locally advanced or metastatic NSCLC when the following criteria are met:
      1. Used as first-line therapy; and
      2. Given in combination with carboplatin or cisplatin; or
    2. Protein-bound paclitaxel is considered medically necessary in the treatment of NSCLC in an individual with confirmed taxane (that is, solvent-based paclitaxel or docetaxel) hypersensitivity.
       
  4. Ovarian Cancer (Epithelial Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer)
    1. Protein-bound paclitaxel is considered medically necessary when used as a single agent in the treatment of persistent or recurrent ovarian cancer (epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer); or
    2. Protein-bound paclitaxel is considered medically necessary in the treatment of persistent or recurrent ovarian cancer (epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer) in an individual with confirmed taxane (that is, solvent-base paclitaxel or docetaxel) hypersensitivity.
       
  5. Pancreatic Cancer

    Protein-bound paclitaxel is considered medically necessary in the treatment of locally advanced or metastatic adenocarcinoma of the pancreas when the following criteria are met:
    1. Used as first-line therapy or later; and
    2. Given in combination with gemcitabine as a single-line of therapy.
       
  6. Uterine/Endometrial Cancer

    Protein-bound paclitaxel is considered medically necessary in the treatment of recurrent, metastatic, or high-risk endometrial cancer in an individual with confirmed taxane (that is, solvent-based paclitaxel or docetaxel) hypersensitivity.
     
  7. Protein-bound paclitaxel is considered medically necessary in the treatment of solid tumors where treatment with a taxane is medically appropriate and the individual has confirmed taxane (that is, solvent-based paclitaxel or docetaxel) hypersensitivity.

Not Medically Necessary:

Protein-bound paclitaxel is considered not medically necessary when the above criteria are not met and for all other indications.

Coding

The following codes for treatments and procedures applicable to this guideline are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

HCPCS

 

J9264

Injection, paclitaxel protein-bound particles, 1 mg [Abraxane]

 

 

ICD-10 Diagnosis

 

C00.0-C80.2

Malignant neoplasms

D00.0-D09.9

In-situ neoplasms

Z85.00-Z85.59

Personal history of malignant neoplasm

Z85.810-Z85.9

Personal history of malignant neoplasm

Discussion/General Information

The FDA Product Information [PI] Label for protein-bound paclitaxel, (Abraxane PI Label, 2015) describes this microtubule inhibitor agent’s mechanism of action as follows:

Abraxane...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. Protein-bound paclitaxel induces abnormal arrays or “bundles” of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis.

Protein-bound paclitaxel (also referred to as albumin-bound paclitaxel or nab-paclitaxel) has received FDA approval in the treatment of the following conditions (Abraxane PI Label, 2015):

The functional properties of protein-bound paclitaxel differ substantially from other formulations; therefore, protein-bound paclitaxel may not be substituted for, or used in combination with, other formulations of conventional paclitaxel.

Breast Cancer

Breast cancer is managed by various treatment modalities including combinations of surgery, radiation therapy, chemotherapy and hormone therapy (National Cancer Institute, 2018). The prognosis and selection of therapies can be affected by clinical and pathologic features of the tumor, reoccurrence and metastatic status.

Protein-bound paclitaxel was first approved by the U.S. Food and Drug Administration (FDA) in January 2005 for use as a single agent (monotherapy) for the treatment of breast cancer in individuals who have metastatic disease refractory to conventional combination chemotherapy or who have experienced relapse within 6 months of adjuvant chemotherapy; prior therapy in these individuals should have included an anthracycline antineoplastic agent (for example, doxorubicin) unless clinically contraindicated.

The current indication for use of protein-bound paclitaxel as a single agent in advanced breast cancer is based primarily on data from two single-arm open label studies (n=106) (Ibrahim, 2005) and a randomized, controlled, comparative study of 460 individuals with metastatic breast cancer (Gradishar, 2005). In the single-arm open label studies, protein-bound paclitaxel was administered at doses of 175 mg/m2 (n=43) and 300 mg/m2 (n=63) (Ibrahim, 2005). Cycles were administered at 3-week intervals. Objective responses were observed in both studies. In the multicenter, randomized, open-label, phase III comparative trial (Gradishar, 2005; Gradishar, 2009), 460 participants with metastatic breast cancer were randomized 1:1 to receive protein-bound paclitaxel at a dose of 260 mg/m2 intravenously (I.V.) over 30 minutes or standard paclitaxel at 175 mg/m2 I.V. over 3 hours with premedication. At study entry, 64% of participants had an impaired ECOG Performance Status score of 1 or 2, 79% had visceral metastases and 76% had greater than three sites of metastases. A total of 14% of the participants did not receive prior chemotherapy, 27% received chemotherapy in the adjuvant setting, 40% in the metastatic setting, and 19% in both metastatic and adjuvant settings. Protein-bound paclitaxel was administered as second or greater than second-line therapy to 59% of participants, with 77% of participants previously exposed to anthracyclines. Participants in the protein-bound paclitaxel arm experienced a significantly higher response rate (RR) (the primary endpoint) compared with standard paclitaxel (33% vs. 19%, respectively; p=0.001) and significantly longer time to tumor progression (23.0 vs. 16.9 weeks, respectively; hazard ratio [HR], 0.75; p=0.006).

The most common adverse reactions (≥ 20%) with single-agent use of protein-bound paclitaxel were alopecia, neutropenia, sensory neuropathy, abnormal electrocardiogram, fatigue/asthenia, myalgia/arthralgia, aspartate aminotransferase (AST) elevation, alkaline phosphatase (ALP) elevation, anemia, nausea, infections, and diarrhea. Sensory neuropathy results in 3% of participants discontinuing treatment. Severe cardiovascular events possibly related to single-agent protein-bound paclitaxel occurred in 3% of participants (Abraxane PI Label, 2015).

Protein-bound paclitaxel has been utilized in the treatment of any breast cancer as a substitute for solvent-based paclitaxel when an individual experiences a documented allergic reaction. This recommendation is based, in part, on a black box warning on the FDA-approved label for solvent-based paclitaxel (Taxol® Injection, HQ Specialty Pharma, Paramus, NJ) which states:

Fatal anaphylaxis and severe hypersensitivity reactions characterized by dyspnea and hypotension requiring treatment, angioedema, and generalized urticaria have occurred in 2 to 4% of patients receiving Taxol in clinical trials. Fatal reactions have occurred in patients despite premedication. Patients who experience severe hypersensitivity reactions to paclitaxel should not be rechallenged with the drug.

The National Comprehensive Cancer Network® (NCCN) Clinical Practice Guideline (CPG) in Oncology for invasive breast cancer (recurrent or metastatic) (V4.2017) states albumin-bound paclitaxel may be used as single agent (“other”) therapy for recurrent or metastatic breast cancer. In addition, albumin-bound paclitaxel may be used in preoperative/adjuvant therapy regimens or chemotherapy regimens for recurrent or metastatic breast cancer as a substitute “…for paclitaxel or docetaxel due to medical necessity (ie, hypersensitivity reaction). If substituted for weekly paclitaxel or docetaxel, then the weekly dose of nab-paclitaxel should not exceed 125 mg/m2.”

Untch and colleagues (2016) evaluated the use of protein-bound paclitaxel compared with solvent-based paclitaxel in a neoadjuvant chemotherapy regimen in a phase III study (GeparSepto-GBG 69) of individuals with previously untreated unilateral or bilateral primary invasive breast cancer (subtype Ki67 and secreted protein acidic and rich in cysteine [SPARC] expression). Participants were women ages 18 years or older with a Karnofsky Performance Status (KPS) index of at least 80%, tumor larger than 2 centimeters without additional risk factors, or between 1 and 2 centimeters (cT1c) with one of the following additional criteria: either clinical or pathological nodal involvement or hormone receptor-negative, or human epidermal growth factor receptor 2 (HER2)-positive, or Ki67 greater than 20%. Participants were randomly assigned to receive weekly protein-bound paclitaxel or weekly solvent-based paclitaxel, both followed by epirubicin plus cyclophosphamide. Participants with HER2-positive tumors received concurrent trastuzumab and pertuzumab every 3 weeks concomitantly with chemotherapy for all cycles. The primary endpoint was pathological complete response (CR), defined as no invasive or non-invasive tumor residuals in breast and axillary lymph nodes after neoadjuvant therapy. Of the 1229 women who were randomly assigned to treatment, a total of 1206 started treatment with protein-bound paclitaxel (n=606) and solvent-based paclitaxel (n=600). A preplanned safety analysis was performed after the sixtieth participant finished taxane therapy, after which time a decision was made to reduce the protein-bound paclitaxel dose due to an unacceptable increase in treatment discontinuation and sensory neuropathy in this group. A total of 444 (73%) participants in the protein-bound paclitaxel group and 477 (80%) in the solvent-based paclitaxel group (p=0.012) completed the taxane, epirubicin, and cyclophosphamide therapy. Pathological CR occurred more frequently in the protein-bound group (n=233 [38%]; 95% confidence [CI], 35-42 participants) than in the solvent-based paclitaxel group (n=174 [29%]; 95% CI, 25-33 participants) (odds ratio [OR] 1.53; 95% CI, 1.20-1.95 [unadjusted p=0.00065]). The incidence of grade 3-4 adverse events was significantly higher in the protein-bound paclitaxel group than in the solvent-based paclitaxel group for anemia (13 [2%] of 605 participants in the protein-bound group vs. 4 [1%] of 601 participants in the solvent-based paclitaxel group; p=0.048) and peripheral sensory neuropathy (63 [10%] participants receiving any protein-bound paclitaxel dose; 31 [8%] of participants starting with 125 mg/m² and 32 [15%] of participants starting with 150 mg/m² vs. 16 [3%] in the solvent-based paclitaxel group; p<0.001). At least one serious adverse event was observed in 283 (23%) participants (156 [26%] in the protein-bound paclitaxel group; 127 [21%] in the solvent-based paclitaxel group; (p=0.057). There were three deaths (during epirubicin plus cyclophosphamide treatment) in the protein-bound paclitaxel group (due to sepsis, diarrhea, and accident unrelated to the trial) compared with one death in the solvent-based paclitaxel group (cardiac failure during paclitaxel treatment). Limitations of this trial include the heterogeneous study population at baseline enrollment (by tumor type and central pathology) and the reduction in protein-bound paclitaxel dose to 125 mg/m² in approximately one-third of the enrolled study participants (resulting in less peripheral sensory neuropathy), although the investigators reported this dose reduction did not affect the frequency of pathological CR; therefore, the overall results for pathological CR are reflective of the lower protein-bound paclitaxel dose. In an exploratory analysis of this study, Furlanetto and colleagues (2017) reported dose reduction with protein-bound paclitaxel (125 mg/m2) were associated with decreased toxicity rates (especially peripheral sensory neuropathy), without influencing pathological CR. A limitation of this analysis is the lack of randomization of participants to protein-bound paclitaxel at doses of 125 mg/m2 or 150 mg/mg2 at study onset, which limits direct comparisons of the long-term efficacy and safety of protein-bound paclitaxel use in the neoadjuvant setting. Additional randomized comparative trials are needed to evaluate the efficacy and safety of protein-bound paclitaxel, in terms of dosing and tolerability, as neoadjuvant chemotherapy in the treatment of early stage breast cancer.

Non-Small Cell Lung Cancer (NSCLC)

NSCLC is any type of epithelial lung cancer other than SCLC, and is classified into two major types: squamous cell carcinoma, which accounts for 25% to 30% of all NSCLC cases and non-squamous cell carcinoma, the most common lung cancer in the U.S. When treatable, surgical resection with curative intent is the primary treatment for lung cancer. Chemotherapy may be used both preoperatively (neoadjuvant chemotherapy) and postoperatively (adjuvant chemotherapy) and as first-line for more advanced stages of lung cancer.

In October 2012, protein-bound paclitaxel was approved by the FDA as first-line treatment of locally advanced or metastatic NSCLC, in combination with carboplatin, in individuals who are not candidates for curative surgery or radiation therapy. The FDA approval was based primarily on the results of a phase III, multicenter, randomized open-label study where individuals with advanced NSCLC received either protein-bound paclitaxel (100 mg/m2) weekly plus carboplatin at under the concentration-time curve (that is, area under the curve [AUC]=6) every 3 weeks (n=521) or solvent-based (sb) (conventional) paclitaxel (200 mg/m2) every 3 weeks plus carboplatin (AUC=6) (n=531) (Socinski, 2012). The study met its primary endpoint demonstrating a statistically significant objective response rate (ORR) for participants in the protein-bound paclitaxel arm compared to those in the sb-paclitaxel arm (33% vs. 25%; RR ratio, 1.313; 95% CI, 1.082 to 1.593; p=0.005). Protein-bound paclitaxel demonstrated a higher ORR as compared to sb-paclitaxel for squamous cell carcinoma histology (41% vs. 24%; RR ratio, 1.680; 95% CI, 1.271 to 2.221; p<0.001) and large cell carcinoma (33% vs. 15%); in addition, protein-bound paclitaxel achieved a similar ORR to sb-paclitaxel in individuals with adenocarcinoma (26% vs. 25%). There was approximately 10% improvement in progression-free survival (PFS) (median, 6.3 vs. 5.8 months; HR, 0.902; 95% CI, 0.767 to 1.060; p=0.214) and overall survival (OS) (OS median, 12.1 vs. 11.2 months; HR, 0.922; 95% CI, 0.797 to 1.066; p=0.271) in the protein-bound paclitaxel arm versus the sb-paclitaxel arm, respectively. North America study participants 70 years of age or older showed a significantly increased OS with protein-bound paclitaxel compared to participants who received sb-paclitaxel.

Significantly less grade ≥ 3 neuropathy, neutropenia, arthralgia, and myalgia occurred in the protein-bound paclitaxel arm, and less thrombocytopenia and anemia occurred in the sb-paclitaxel arm. The most common adverse reactions (≥ 20%) when protein-bound paclitaxel was used in combination with carboplatin for NSCLC were alopecia, anemia, fatigue, nausea, neutropenia, peripheral neuropathy, and thrombocytopenia (Abraxane PI Label, 2015).

The NCCN CPG for NSCLC (V3.2018) includes a category 2A recommendation (based upon lower-level evidence [Fang, 2014] and uniform NCCN consensus that the intervention is appropriate) for use of protein-bound paclitaxel in combination with platinum-based therapy for individuals with advanced, metastatic, incurable NSCLC, stating “cisplatin or carboplatin have been proven effective in combination with many of the following agents...” including albumin-bound paclitaxel.” In addition, the CPG includes a category 2A recommendation for use of protein-bound paclitaxel as a substitute for solvent-based paclitaxel or docetaxel stating, “Albumin-bound paclitaxel may be substituted for either paclitaxel or docetaxel in patients who have experienced hypersensitivity reactions after receiving paclitaxel or docetaxel despite premedication, or for patients were the standard premedications (ie, dexamethasone, H2 blockers, H1 blockers) are contraindicated).”

Pancreatic Cancer

Adenocarcinoma of the pancreas is a tumor that metastasizes (spreads) within the abdomen to the liver, lungs, bone, and brain. These cancers cannot be removed by surgery. Chemotherapy is considered the primary treatment of adenocarcinoma of the pancreas, is not curative, but may shrink or slow the growth of these tumors. Rates of pancreatic cancer have been fairly stable over the past several years.

In September 2013, the FDA approved protein-bound paclitaxel for use in the treatment of metastatic adenocarcinoma of the pancreas as first-line treatment, in combination with gemcitabine. Combination therapy has been associated with higher response rates and prolonged OS and PFS compared with single-agent gemcitabine. The clinical effectiveness of protein-bound paclitaxel was evaluated in a multicenter, multinational, randomized, open-label study (MPACT trial) comparing protein-bound paclitaxel plus gemcitabine to gemcitabine monotherapy as first-line treatment of metastatic adenocarcinoma of the pancreas (Von Hoff, 2013). Study participants included those individuals with KPS ≥ 70, normal bilirubin levels, transaminase levels ≤ 2.5 times the upper limit of normal (ULN) or ≤ 5 times the ULN for individuals with liver metastasis, no prior cytotoxic chemotherapy in the adjuvant setting or for metastatic disease, no ongoing active infection requiring systemic therapy, and no history of interstitial lung disease. A total of 861 participants were randomized (1:1) to receive protein-bound paclitaxel plus gemcitabine (n=431) or gemcitabine (n=430). Randomization was stratified by geographic region (Australia, Western Europe, Eastern Europe, or North America), KPS (70 to 80 vs. 90 to 100), and presence of liver metastasis (yes vs. no). In the intention-to-treat (all randomized) population, the median age was 63 years (range 27-88 years) with 42% ≥ 65 years of age and KPS was 90-100 in 60%. Disease characteristics included 46% of participants with three or more metastatic sites and 84% of participants with liver metastasis. Participants randomized to the protein-bound paclitaxel plus gemcitabine arm received 125 mg/m2 I.V. infusion over 30-40 minutes followed by gemcitabine 1000 mg/m2 I.V. infusion over 30-40 minutes on days 1, 8, and 15 of each 28-day cycle. Participants randomized to the gemcitabine arm received 1000 mg/m2 I.V. infusion over 30-40 minutes 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. Participants in both arms received treatment until disease progression or unacceptable toxicity. The primary outcome measure was OS; additional outcome measures were PFS and ORR. The median OS was 8.5 months in the protein-bound paclitaxel plus gemcitabine group compared to 6.7 months in the gemcitabine group (HR for death, 0.72; 95% CI, 0.62 to 0.83; p<0.001). The OS rate at 1 year was 35% in the protein-bound paclitaxel plus gemcitabine group compared to 22% in the gemcitabine group and 9% versus 4% at 2 years. The median PFS was 5.5 months in the protein-bound plus gemcitabine group compared to 3.7 months in the gemcitabine group (HR for disease progression or death, 0.69; 95% CI, 0.58 to 0.82; p<0.001); the ORR according to an independent reviewer was 23% versus 7% in the 2 groups (p<0.001). The addition of protein-bound paclitaxel also improved other endpoints, including 1-year survival, 2-year survival, response rate, and PFS. OS was associated with a decrease in CA 19-9 (HR, 0.53; 95% CI, 0.36-0.78; p=0.001) (Chiorean, 2016). The most common adverse events of grade 3 or higher were neutropenia (38% in the protein-bound paclitaxel plus gemcitabine group vs. 27% in the gemcitabine group), fatigue (17% vs. 7%), and neuropathy (17% vs. 1%). Febrile neutropenia occurred in 3% versus 1% of the participants in the 2 groups. In the protein-bound paclitaxel plus gemcitabine group, neuropathy of grade 3 or higher improved to grade 1 or lower in a median of 29 days (Abraxane PI Label, 2015; Van Hoff, 2015). In exploratory analyses conducted in clinically relevant subgroups with a sufficient number of subjects, the treatment effects on OS were similar to that observed in the overall study population (Hosein, 2013).

Goldstein and colleagues (2015) reported results of long-term survival with gemcitabine plus protein-bound paclitaxel in participants from the MPACT trial. A total of 3% of participants in the treatment arm were alive at 42 months, compared to no living participants in the control arm at that time. Factors that were associated with survival in the MPACT trial included KPS score and absence of liver metastases (Tabernero, 2015).

Off-FDA Label Uses of Protein-bound Paclitaxel

Malignant Melanoma

Melanoma is a malignant tumor of melanocytes, which are the cells that make the pigment melanin and are derived from the neural crest. Although most melanomas arise in the skin, they may also arise from mucosal surfaces or at other sites to which neural crest cells migrate, including the uveal tract. Malignant melanoma of the skin is also referred to as cutaneous melanoma. Melanoma is the most common cancer in young adults aged 25 to 29 years and the second most common cancer in those aged 15 to 29 years (National Cancer Institute [NCI], 2017).

The NCCN CPG for melanoma (V2.2018) includes a category 2A recommendation for use of protein-bound (albumin-bound or nab-paclitaxel) paclitaxel as a cytotoxic regimen for metastatic disease (“Other Systemic Therapies”), although, “In general, options for front-line therapy for metastatic melanoma include immunotherapy or targeted therapy.” The CPG recommendation is based on data from two phase II clinical trials where protein-bound paclitaxel yielded RR of 22% to 26% among chemotherapy-naive individuals with metastatic melanoma (Hersh, 2010; Kottschade, 2011).

Hersh and colleagues (2010) evaluated the effectiveness and safety of protein-bound paclitaxel in previously treated and chemotherapy-naive individuals with histologically or cytologically measureable metastatic melanoma. Protein-bound paclitaxel was administered weekly for 3 of 4 weeks at a dose of 100 mg/m2 I.V. in previously-treated participants (n=37) or 150 mg/m2 I.V. in chemotherapy-naive participants (n=37). The RR was 2.7 % (1 of 37 participants; 95% CI, 0.1%-14.2%) in the previously treated arm and 21.6% (8 of 37 participants; 95% CI, 8.4%-34.9%) in chemotherapy-naive participants. The duration of response for the previously treated participants was 12.9 months; for the chemotherapy-naive participants, the median duration of response was 24.9 months. An additional 13 (35%) of the previously treated participants and 10 (27%) of the chemotherapy-naive participants had stable disease for at least 16 weeks. The median PFS was 3.5 months (95% CI, 1.7-5.6 months) and 4.5 months (95% CI, 3.4-6.7 months), and the median OS was 12.1 months (95% CI, 6.5-17.5 months) and 9.6 months (95% CI, 6.7-23.7 months) in the previously treated and chemotherapy-naive cohorts, respectively. Approximately 78% of the previously treated participants and 49% of the chemotherapy-naive participants were treated without dose reduction. A total of 8 (22 %) chemotherapy-naive participants discontinued therapy because of toxicity, usually neuropathy or myelosuppression. Grade 3 or 4 neutropenia was experienced by 41% and 14% of participants in the chemotherapy-naive and previously treated groups, respectively; additional treatment-emergent and treatment-related toxicities included alopecia, neuropathy, and fatigue.

Kottschade and colleagues (2011) evaluated the clinical effectiveness and safety of protein-bound paclitaxel in individuals with unresectable stage IV melanoma. The study consisted of two parallel phase II cohorts who were chemotherapy-naive or previously treated. Eligible participants were 18 years of age or older with unresectable, histologically confirmed stage IV melanoma as defined by the Response Evaluation Criteria in Solid Tumors (RECIST), ECOG Performance Status of 0 to 2, life expectancy ≥ 3 months, adequate hematologic and hepatic function, and ≥ 4 weeks since the last chemotherapy (previously treated cohort), radiation therapy, or immunotherapy. Treatment consisted of protein-bound paclitaxel administered by I.V. infusion at 100 mg/m2 followed by carboplatin (with a target AUC of 2) administered over 30 minutes on days 1, 8, and 15 of a 28-day cycle. If participants did not develop excessive toxicity or progressive disease, treatment beyond 8 cycles was at the discretion of the treating physician. The primary endpoint was the ORR, defined as the number of eligible participants whose disease met RECIST criteria for response. For those participants whose disease responded to treatment, the duration of response was defined as “the time from the first tumor evaluation, when an objective status of CR or partial response (PR) was assigned, to date of disease progression.” A total of 76 participants (41 chemotherapy-naive and 35 previously treated) were enrolled and 3 participants withdrew consent prior to starting treatment. The median number of treatment cycles administered was four. Dose reductions and dose omissions were primarily related to severe neutropenia and neuropathy. A total of 28 individuals discontinued study participation due to disease progression, with one treatment-related death. There were 10 (25.6%) responses (1 CR and 9 PR) in the chemotherapy-naive group (90% CI, 16.7% to 42.3%) and 3 (8.8%) responses (3 PR) in the previously treated (90% CI, 2.5% to 21.3%). Median PFS was 4.5 months in the chemotherapy-naive cohort and 4.1 months in the previously treated group. Median OS was 11.1 months in the chemotherapy-naive group and 10.9 months in the previously treated group. Severe toxicities in both groups (greater ≥ grade 3) included neutropenia, thrombocytopenia, neurosensory problems, fatigue, nausea, and vomiting.

Ovarian Cancer (Epithelial Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer)

According to the NCI (2018) epithelial carcinoma of the ovary is one of the most common gynecologic malignancies and the fifth most frequent cause of cancer death in women, with 50% of all cases occurring in women older than 65 years. Epithelial ovarian cancer comprises the majority of malignant ovarian neoplasms (about 90%); however, less common pathologic subtypes may occur (NCCN, 2018).

The NCCN CPG (V2.2018) includes category 2A off-label recommendations for use of protein-bound paclitaxel as a potentially active agent in persistent or recurrent ovarian cancer (including epithelial ovarian cancer, fallopian tube cancer, primary peritoneal cancer, and less common histopathologies) when used as a single agent. The NCCN acknowledges that many of the single agents have not been tested in individuals “who have been treated with modern chemotherapy regimens.” Protein-bound paclitaxel is also useful in certain circumstances in combination with carboplatin in platinum-sensitive individuals with confirmed taxane hypersensitivity. The recommendation for single-agent protein-bound paclitaxel is based in part on general consensus and data in the peer-reviewed medical literature including two phase II studies where an ORR of 64% was reported with use of single-agent protein-bound paclitaxel for recurrent ovarian cancer (Coleman, 2011; Teneriello, 2009). The category 2A recommendation for use of protein-bound paclitaxel in combination with carboplatin in platinum-sensitive individuals with confirmed taxane hypersensitivity is based on uniform NCCN consensus that the intervention is appropriate. The NCCN CPG states that in gynecologic oncology treatment, some drugs more commonly cause adverse reactions including, but not limited to, docetaxel and solvent-based paclitaxel. Adverse reactions associated with these taxanes agents tend to be infusion-related, are often contributed to cremophor in paclitaxel, and tend to occur during the first few cycles of treatment, but may occur regardless of how many previous cycles were administered. Most of these adverse drug reactions are mild, but more severe reactions may occur with platinum and taxane drugs, including anaphylaxis, which can be life-threatening. The treating clinician should consider switching to protein-bound paclitaxel “due to medical necessity (i.e., hypersensitivity reaction), or consider switching to docetaxel; however, there are no data to support switching taxanes. Cross reactions have occurred and have been life-threatening.” 

Teneriello and colleagues (2009) evaluated the effectiveness and safety of protein-bound paclitaxel in a phase II, open-label study of 47 individuals (44 evaluable participants) with recurrent platinum-sensitive, histologically or cytologically confirmed measurable epithelial cancer of the ovary, fallopian tube, or peritoneum cancer (any stage, grade 2 to 3 if stage I) according to RECIST or an elevated CA-125 (> 70 U/mL) in persons without measurable disease. Participants were administered protein-bound paclitaxel at 260 mg/m2 I.V. for 30 minutes on day 1 of a 21-day cycle for six cycles or until disease progression. The median age of participants was 65.5 years; 76% had stage IIIC or IV disease, 81% had ECOG Performance Status of 0, and 94% had prior surgery. Treatment outcomes were assessed with RECIST, CA-125, or both methods (if applicable). The ORR was 64% (15 CR and 13 PR among 44 assessable participants). In participants evaluated with RECIST only, the ORR was 45% (CR, 1 of 11; PR, 4 of 11). In participants with only elevated CA-125, the ORR was 82% (CR, 7 of 11; PR, 2 of 11). In participants meeting both RECIST and CA-125 criteria, the ORR was 64% (CR, 7 of 22; PR, 7 of 22). The median time to response was 1.3 months (range, 0.5 to 4.8 months), the median duration of the best response was 7.9 months, and the estimated median PFS was 8.5 months. Two participants withdrew from the study because of neuropathy. The most frequent grade 3 to 4 treatment-related toxicities reported as “mild to moderate and manageable” were neutropenia (24%) and neuropathy (9%).

Coleman and colleagues (2011) evaluated the efficacy and safety of protein-bound paclitaxel in a phase II study of 51 individuals (47 evaluable participants) with platinum- and taxane-resistant ovarian cancer, defined as persistent or progressive disease following primary chemotherapy (n=5) or recurrence within 6 months of treatment completion (n=42). The median age of participants was 59 years (range, 34-78), 72% had serous histology, 81% had high-grade disease, and all participants had no prior therapy for recurrent disease and a Gynecologic Oncology Group Performance Status of ≤ 2. Protein-bound paclitaxel was administered at 100 mg/m² I.V. on days 1, 8, and 15 on a 28-day schedule. Treatment modifications, including dose reductions and a delay in therapy (for a maximum of 2 weeks), were allowed for hematologic toxicity based on absolute neutrophil counts (ANCs). Dose reductions and delay in subsequent therapy was allowed for specific grade 2 (or greater) non-hematologic toxicities. The primary endpoint was frequency of objective tumor response. Secondary endpoints included frequency and severity of adverse effects, and duration of PFS and OS. The median number of cycles administered was 4 (range, 1-40) and the most common reason for treatment discontinuation was disease progression occurring in 42 (82%) of participants. Treatment-associated toxicity, physician preference and participant preference accounted for an additional 3 (6%), 3 (6%) and 2 (4%) treatment discontinuations, respectively. Of the 47 evaluable participants, 1 CR and 10 PRs were confirmed (23%); 17 participants (36%) had stable disease. The median PFS was 4.5 months (95% CI, 2.2-6.7); OS was 17.4 months (95% CI, 13.2-20.8). A total of 17 participants (36%) had PFS > 6 months. There were no grade 4 toxicities observed; grade 3 toxicities included neutropenia (n=6), anemia (n=3), gastrointestinal (n=2), metabolic (n=2), pain (n=2), and leukopenia (n=1). Neurosensory toxicity was observed as grade 2 in 5 participants and grade 3 in 1 participant.

In the absence of a randomized controlled trial, the data from these two studies supports the NCCN 2A recommendation for use of single-agent protein-bound paclitaxel in a cohort of individuals with persistent or recurrent ovarian cancer.

Uterine/Endometrial Cancer

According to the NCCN CPG for uterine neoplasms (V1.2018), adenocarcinoma of the endometrium (also known as endometrial cancer, or more broadly as uterine cancer or carcinoma of the uterine corpus) is the most common female genital tract malignancy in the United States, with an estimated 61,380 new uterine cancer cases in 2017 and 10,920 deaths resulting from the disease. In 2017, 67% of individuals with adenocarcinoma of the endometrium were diagnosed with the disease confined to the uterus at diagnosis, with regional and distant disease comprising 21% and 8% of cases, respectively (NCI, 2017).

The NCCN CPG for uterine cancer (V1.2018) includes a category 2A recommendation for use of protein-bound paclitaxel as single agent systemic chemotherapy for individuals with recurrent, metastatic, or high-risk endometrial carcinoma who are hypersensitive to paclitaxel, with a strong recommendation for participation in a clinical trial. If multiagent chemotherapy regimens are contraindicated, the NCCN recommendation states:

Albumin-bound paclitaxel is a reasonable substitute for patients with a hypersensitivity to paclitaxel if the skin testing to paclitaxel is negative. If the patient has a positive skin test to paclitaxel then the patient requires desensitization to paclitaxel. Albumin-bound paclitaxel is not a reasonable substitute for paclitaxel if the patient’s skin test is positive.

The NCCN recommendation is based on consensus that the intervention is appropriate; to date, no peer-reviewed publications were cited with this recommendation. The evidence in the peer-reviewed medical literature evaluating the use of protein-bound paclitaxel following hypersensitivity reaction to solvent-based paclitaxel consists of small case series and a large single-institution study.

Maurer and colleagues (2017) reported on a retrospective case series of 37 women with gynecologic cancers (n=22, ovarian cancer; n=12, endometrial cancer; n=2 uterine sarcoma; and n=1, cervical cancer) with a history of solvent-based paclitaxel hypersensitivity reaction who received protein-bound paclitaxel. A total of 6 women (16.2%) had a prior hypersensitivity reaction to both solvent-based paclitaxel and docetaxel while the other 31 (83.8%) women had not received docetaxel. No women experienced a hypersensitivity reaction to protein-bound paclitaxel. The authors acknowledge that this retrospective cohort of women included various histologies and stages of disease who received treatment in both the adjuvant and recurrent setting. “Therefore, we are unable to draw conclusions about the efficacy of nab-paclitaxel.” They suggested, however, the results of two prospective phase II studies of protein-bound paclitaxel in recurrent ovarian, fallopian tube, and primary peritoneal cancer (Coleman, 2011; Teneriello, 2009) and one phase II trial of protein-bound paclitaxel in recurrent or persistent cervix cancer (Alberts, 2012) showed activity of the drug with ORR of 64% (platinum sensitive) and 23% (platinum resistant).

Fader and colleagues (2009) reported on use of protein-bound paclitaxel in the treatment of 5 women with gynecologic cancers (n=2, ovarian; n=2, endometrial; n=1, cervical) with severe hypersensitivity reactions to solvent-based paclitaxel. In all 5 women, protein-bound paclitaxel was well tolerated with no reactions or major side effects to the drug. In a large single-institution study, Markman and colleagues (2000) reported an incidence of at least one clinically significant hypersensitivity reaction in approximately 9% (44 of 450) of women treated with solvent-based paclitaxel for gynecologic cancers. All 43 women (plus an additional 4 women referred to the institution after having previously experienced a severe paclitaxel-associated hypersensitivity reaction at another institution) were retreated with solvent-based paclitaxel and subsequently able to receive the agent. Five women required treatment with a standardized desensitization regimen, developed by the institution, to successfully receive solvent-based paclitaxel. One woman, described as having a poor performance status and a pseudoanaphylactoid-type reaction (severe hypotension and respiratory compromise), was not readministered solvent-based paclitaxel. The authors suggested that in individuals with gynecologic cancers who have mild-to-severe, nonanaphylactoid reactions to solvent-based paclitaxel, “it is reasonable to offer them a rechallenge of the drug”; however, it is less clear whether individuals with pseudoanaphylactoid-type reactions to solvent-based paclitaxel or those who experience a second hypersensitivity reaction should be reexposed to this agent.

In a review article, Picard and colleague (2015) suggest that taxane skin testing, which identifies individuals with an IgE-mediated sensitivity, may be a “promising diagnostic and risk stratification tool in the management of patients with hypersensitivity reactions (HSRs) to taxanes,” stating:

...risk stratification and re-exposure could be performed either through rapid drug desensitization or graded challenge based on the severity of the initial HSR and the skin test result. Rapid drug desensitization has been shown to be an effective and safe method to re-introduce taxanes in hundreds of patients, including those with life-threatening HSRs. Patients with non-severe delayed skin HSRs may benefit from rapid drug desensitization since they may be at increased risk for an immediate HSR upon re-exposure.

Other Uses of Protein-bound Paclitaxel

Urothelial Carcinoma

Bladder cancers are divided into several types and may respond differently to treatments. More than 90% of bladder cancers are urothelial (transitional cell) carcinoma which occurs in the urinary tract system, involving the renal pelvis to the proximal urethra. According to the NCI (2017), bladder cancer is the sixth most common cancer in the U.S., the third most common cancer in men, but only the eleventh most common cancer in women.

The NCCN CPG for bladder cancer (V3.2018) includes a category 2A recommendation for use of protein-bound paclitaxel as a single agent, subsequent systemic therapy (post-platinum or post-checkpoint inhibitor regimens), and an alternate regimen (other recommended regimens) for select individuals with locally advanced or metastatic urothelial carcinoma of the bladder (Stage IV). The NCCN states “Data for subsequent-line systemic therapy for locally advanced or metastatic disease are highly variable” and recommend enrollment in a clinical trial. “The available options depend on what was offered as first line.” The NCCN recommendation considers outcomes of an open-label, single-group, two-stage, phase II study of 48 individuals who had documented progression on or within 12 months of a first-line platinum containing regimen for locally advanced or metastatic urothelial cancer (Ko, 2013). Participants received single agent protein-bound paclitaxel at 260 mg/m2 I.V. every 3 weeks until disease progression or occurrence of unacceptable toxic effects. The primary endpoint was objective tumor response defined by a CR or PR according to RECIST criteria. Participants received a median of six cycles (range, 1 to 15). Of the 47 evaluable participants, 1 (2.1%) participant had a CR and 12 (25.5%) participants had PRs, resulting in an overall response of 27.7% (95% CI, 17.3-44.4). Median PFS was 6 months (95% CI, 3.9-8.5), and median OS was 10.8 months (5.8-16.9). The most frequently reported grade 3 or higher toxic effects were pain, fatigue, hypertension, joint pain, and neuropathy; no treatment-related deaths occurred. Limitations of this study include the small sample size and lack of a randomized control group.

In contrast to the reasonable tolerability profile and efficacy reported in the Ko (2013) trial of single agent protein-bound paclitaxel, Alva and colleagues (2014) reported that combination therapy of protein-bound paclitaxel with carboplatin and gemcitabine was poorly tolerated as first-line therapy in a high risk population of individuals with advanced urothelial cancer. Participants had confirmed metastatic, locally recurrent of advanced pure or mixed urothelial cancer, ECOG Performance Status of 0-2, no prior chemotherapy for current disease stage, and no taxane for greater than or equal to 1 year. Therapy consisted of protein-bound paclitaxel at 220 mg/m2 with optional dose escalation to 260 mg/m2 for subsequent cycles, with carboplatin AUC 5 on day 1 and gemcitabine on days 1 and 8 in 21-day cycles. Dose modifications in all three drugs to -1 and -2 levels were allowed for toxicity. The primary endpoint was overall response rate (CR+PR) by RECIST 1.0 criteria. Secondary endpoints were safety, PFS and OS. A total of 16 participants were enrolled due to poor accrual. Thirteen participants had metastatic disease, 3 participants were women, and the median age was 73.9 years (range 51.3-83). ECOG Performance Status was 0 in 4 (25.0%) and 1 in 11 (68.8%) participants. A total of 11 of 16 (68.8%) participants were removed from study protocol due to toxicity (severe cytopenias/myelosuppression), of which 7 participants began other therapies before progression was documented and 1 participant withdrew consent. The ORR included 1 (6.3%) participant who had a confirmed PR response among the 15 evaluable participants. Two participants (13.3%) had unconfirmed PR. The median PFS was 11.2 months (95% CI, 2.0-11.2 months). Median OS was 13.1 months (95% CI, 9.8-19.6 months). The number of treatment cycles ranged from 1 to 8 with a median of 3. Median PFS follow-up was 5.1 months (range, 1-11.2 months) and median survival follow-up was 13.1 months (range, 2-21 months). The investigators noted that the hematologic toxicity encountered with combination therapy or protein-bound paclitaxel, carboplatin and gemcitabine in this trial was more severe than their clinical experience with the same combination in a neoadjuvant trial conducted concurrently at their institution, where all but 3 of the 26 participants received all three cycles intended with similar doses (Grivas, 2013); however, the investigators suggested the neoadjuvant population with bladder cancer “is a much more robust group in terms of the ability to tolerate cytotoxic chemotherapy than advanced bladder cancer patients who have a greater burden of disease, inferior performance status and poor renal function.” Limitations of this study include the small sample size and high withdrawal rate, which “…rendered pointless any attempt at assessment of the regimen’s efficacy.”

In summary, additional well-designed, controlled studies evaluating alternative dosing schedules for protein-bound paclitaxel compared with other chemotherapy regimens are needed to determine its net health benefit, as a single-agent or in combination therapy, for locally advanced or metastatic urothelial cancer.

Other Proposed Uses

Protein-bound paclitaxel has been studied or is currently being studied as a single agent or in combination with other chemotherapeutic agents for the treatment of other cancers, including use as first-line therapy for HER2-negative metastatic breast cancer (Lobo, 2010; Mirtsching, 2011), adrenocortical cancer (Demeure, 2012), advanced solid tumors (Abu-Khalaf, 2015), angiosarcoma (Hirata, 2011), cancer of unknown primary (CUP), cervical cancer (Alberts, 2012; Li, 2017), esophageal cancer (Fan, 2016; Shi, 2013), gastric cancer (Koizumi, 2015), head and neck cancer (including squamous-cell carcinoma of the esophagus, hypopharynx, nasopharyngeal, oropharynx, and oral cavity) (Adkins, 2013; Adkins, 2016; Damascelli, 2007; Huang, 2016), hepatocellular cancer, prostate cancer (Shepard, 2009), and small cell lung cancer (Grilley-Olson , 2015). Limitations of some of these studies include lack of a randomized comparator group and small study populations. To date, the FDA has not approved protein-bound paclitaxel for use in the treatment of any of these conditions.

FDA PI Label Information for Abraxane

Black Box warnings from the FDA PI label for Abraxane (2015) include the following:

Warning: Neutropenia

Contraindications

Warnings and Precautions

*Note: Refer to the FDA PI label (Abraxane, 2015) Section 2.5 Dose Reduction/Discontinuation Recommendations for additional information.

Drug Interactions

Definitions

Adjuvant therapy: Treatment given after the primary treatment to increase the chances of a cure; may include chemotherapy, radiation, hormone, or biological therapy.

Complete response (CR): The disappearance of all signs of cancer as a result of treatment; also called complete remission; does not indicate the cancer has been cured.

Eastern Cooperative Oncology Group (ECOG) Performance Status: A scale used to assess how an individual's disease is progressing, determine how the disease affects the daily living abilities of the individual, and determine appropriate treatment and prognosis (Oken, 1982):

Grade

ECOG PERFORMANCE STATUS

0

Fully active, able to carry on all pre-disease performance without restriction

1

Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work

2

Ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours

3

Capable of only limited self-care; confined to bed or chair more than 50% of waking hours

4

Completely disabled; cannot carry on any self-care; totally confined to bed or chair

5

Dead

Hypersensitivity: An excessive or abnormal sensitivity to a substance. A person who is hypersensitive to a certain drug may suffer a severe allergic reaction if given the drug.

Line of therapy:

Metastasis: A cancer that has spread from one part of the body to another; a metastatic tumor contains cells that are like those in the original (primary) tumor and have spread beyond the local lymph nodes; also referred to as stage IV cancer.

Microtubule inhibitor agent: Microtubules help support the shape of a cell and chromosome movement during cell division, and assist cell organelles to move inside the cell. Certain anticancer drugs keep microtubules from working, that is, inhibit mitosis or cell division.

Neoadjuvant therapy: Treatment given as a first step to shrink a tumor before the main treatment (usually surgery) is given. Examples of neoadjuvant therapy include chemotherapy, radiation therapy, and hormone therapy; a type of induction therapy.

Objective response rate (ORR): The proportion of participants in a clinical trial with a tumor size reduction of a predefined amount and for a minimum period of time.

Partial response (PR): A decrease in the size of a tumor, or in the amount of cancer in the body, resulting from treatment; also called partial remission.

Platinum-sensitive: A type of cancer (such as ovarian cancer) that responds to chemotherapy with a platinum-containing drug (such as, carboplatin or cisplatin). Even if the cancer recurs after treatment, platinum-sensitive ovarian cancer may respond again to treatment with a platinum-taxane combination.

Progression-free survival (PFS): The length of time during and after treatment that an individual lives but does not get worse (usually measured by the size of a tumor or amount of cancer in the body).

Refractory disease: Illness or disease that does not respond to treatment.

Relapsed disease: After a period of improvement, the return of signs and symptoms of illness or disease.

Single line of therapy: One line of therapy.

Taxane: A chemotherapy drug (such as docetaxel or paclitaxel) commonly used in the treatment of ovarian cancer.

Unresectable: Unable to be removed with surgery.

References

Peer Reviewed Publications:

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  21. Grivas PD, Hussain M, Hafez K, et al. A phase II trial of neoadjuvant nab-paclitaxel, carboplatin, and gemcitabine (ACaG) in patients with locally advanced carcinoma of the bladder. Urology. 2013; 82(1):111-117.
  22. Hersh EM, 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):155-163.
  23. Hirata T, Yonemori K, Ando M, et al. Efficacy of taxane regimens in patients with metastatic angiosarcoma. Eur J Dermatol. 2011; 21(4):539-545.
  24. Hirsh V, Okamoto I, Hon JK, et al. Patient-reported neuropathy and taxane-associated symptoms in a phase 3 trial of  nab-paclitaxel plus carboplatin versus solvent-based paclitaxel plus carboplatin for advanced non-small-cell lung cancer. J Thorac Oncol. 2014; 9(1):83-90.
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  27. Huang Y, Liang W, Yang Y, et al. Phase I/II dose-finding study of nanoparticle albumin-bound paclitaxel (nab®-paclitaxel) plus cisplatin as treatment for metastatic nasopharyngeal carcinoma. BMC Cancer. 2016; 16:464.
  28. Ibrahim NK, Samuels B, Page R, et al. Multicenter phase II trial of ABI-007, an albumin-bound paclitaxel, in women with metastatic breast cancer. J Clin Oncol. 2005; 23:6019-6026.
  29. Ko YJ, Canil CM, Mukherjee SD, et al. 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.
  30. Koizumi W, Morita S, Sakata Y. A randomized Phase III trial of weekly or 3-weekly doses of nab-paclitaxel versus weekly doses of Cremophor-based paclitaxel in patients with previously treated advanced gastric cancer (ABSOLUTE Trial). Jpn J Clin Oncol. 2015; 45(3):303-306.
  31. Kottschade LA, Suman VJ, Amatruda T 3rd, et al. 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.
  32. Li Y, Zeng J, Huang M, et al. A phase 2 study of nanoparticle albumin-bound paclitaxel plus nedaplatin for patients with advanced, recurrent, or metastatic cervical carcinoma. Cancer. 2017; 123(3):420-425.
  33. Lobo C, Lopes G, Baez O, et al. Final results of a phase II study of nab-paclitaxel, bevacizumab, and gemcitabine as first-line therapy for patients with HER2-negative metastatic breast cancer. Breast Cancer Res Treat. 2010; 123(2):427-435.
  34. Loong HH, Winquist E, Waldron J, et al. Phase 1 study of nab-paclitaxel, cisplatin and 5-fluorouracil as induction chemotherapy followed by concurrent chemoradiotherapy in locoregionally advanced squamous cell carcinoma of the oropharynx. Eur J Cancer. 2014; 50(13):2263-2270.
  35. Markman M, Kennedy A, Webster K, et al. Paclitaxel-associated hypersensitivity reactions: experience of the gynecologic oncology program of the Cleveland Clinic Cancer Center. J Clin Oncol. 2000; 18(1):102-105.
  36. Maurer K, Michener C, Mahdi H, Rose PG. Universal tolerance of nab-paclitaxel for gynecologic malignancies in patients with prior taxane hypersensitivity reactions. J Gynecol Oncol. 2017; 28(4):e38.
  37. McKiernan JM, Barlow LJ, Laudano MA, et al. A phase I trial of intravesical nanoparticle albumin-bound paclitaxel in the treatment of bacillus Calmette-Guerin refractory nonmuscle invasive bladder cancer. J Urol. 2011; 186(2):448-451.
  38. Mirtsching B, Cosgriff T, Harker G, et al. Phase II study of weekly nanoparticle albumin-bound paclitaxel with or without trastuzumab in metastatic breast cancer. Clin Breast Cancer. 2011; 11(2):121-128.
  39. 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.
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  41. Reynolds C, Barrera D, Jotte R, et al. Phase II trial of nanoparticle albumin-bound paclitaxel, carboplatin, and bevacizumab in first-line patients with advanced nonsquamous non-small cell lung cancer. J Thorac Oncol. 2009; 4(12):1537-1543.
  42. 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.
  43. Satouchi M, Okamoto I, Sakai H et al. Efficacy and safety of weekly nab-paclitaxel plus carboplatin in patients with advanced non-small cell lung cancer. Lung Cancer. 2013; 81:97-101.
  44. Shepard DR, Dreicer R, Garcia J, et al. Phase II trial of neoadjuvant nab-paclitaxel in high risk patients with prostate cancer undergoing radical prostatectomy. J Urol. 2009; 181(4):1672-1677; discussion 1677.
  45. Shi Y, Qin R, Wang ZK, Dai GH. Nanoparticle albumin-bound paclitaxel combined with cisplatin as the first-line treatment for metastatic esophageal squamous cell carcinoma. Onco Targets Ther. 2013; 6:585-591.
  46. Socinski MA, Bondarenko I, Karaseva NA, et al. 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; 30:2055-2062.
  47. Socinski MA, Okamoto I, Hon JK, et al. Safety and efficacy analysis by histology of weekly nab-paclitaxel in combination with carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer. Ann Oncol. 2013; 24(9):2390-2396.
  48. Tabernero J, Chiorean EG, Infante JR, et al. Prognostic factors of survival in a randomized phase III trial (MPACT) of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with metastatic pancreatic cancer. Oncologist. 2015; 20:143-150.
  49. Teneriello MG, Tseng PC, Crozier M, et al. Phase II evaluation of nanoparticle albumin-bound paclitaxel in platinum-sensitive patients with recurrent ovarian, peritoneal, or fallopian tube cancer. J Clin Oncol. 2009; 27(9):1426-1431.
  50. Untch M, Jackisch C, Schneeweiss A, et al. Nab-paclitaxel versus solvent-based paclitaxel in neoadjuvant chemotherapy for early breast cancer (GeparSepto-GBG 69): a randomised, phase 3 trial. Lancet Oncol. 2016; 17(3):345-356.
  51. Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013; 369:1691-1703.
  52. Von Hoff DD, Ramanathan RK, Borad MJ, et al. Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced pancreatic cancer: a phase I/II trial. J Clin Oncol. 2011; 29(34):4548-4554.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. Abraxane [Product Information]. Summit, NJ. Abraxis BioScience, LLC., Celgene Corp.; July 2015. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021660s041lbl.pdf. Accessed on April 5, 2018.
  2. National Comprehensive Cancer Network®. NCCN Drugs & Biologic Compendium™ (electronic version). For additional information visit the NCCN website: http://www.nccn.org. Accessed on April 5, 2018.
  3. NCCN Clinical Practice Guidelines in Oncology®. © 2017-2018 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website at: http://www.nccn.org/index.asp. Accessed on April 5, 2018.
    • Bladder Cancer (V3.2018). Revised March 14, 2018.
    • Breast Cancer (V4.2017). Revised February 7, 2018.
    • Melanoma (V2.2018). Revised January 19, 2018.
    • Non-Small Cell Lung Cancer (V3.2018). Revised February 21, 2018.
    • Ovarian Cancer (including Fallopian Tube Cancer and Primary Peritoneal Cancer) (V2.2018). Revised March 9, 2018.
    • Pancreatic Adenocarcinoma (V3.2017). Revised September 11, 2017.
    • Uterine Cancer (V1.2018). Revised October 13, 2017.
  4. Paclitaxel, protein-bound. In: DrugPoints® System (electronic version). Truven Health Analytics, Greenwood Village, CO. Updated March 20, 2018. Available at: http://www.micromedexsolutions.com. Accessed on April 5, 2018.
  5. Paclitaxel (Protein Bound) Monograph. Lexicomp® Online, American Hospital Formulary Service® (AHFS®) Online, Hudson, Ohio, Lexi-Comp., Inc. Last revised August 10, 2017. Accessed on April 5, 2018.
  6. Taxol Injection [Product Information]. Paramus, NJ. HQ Specialty Pharma; March 3, 2015. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020262s051lbl.pdf. Accessed on April 5, 2018.
Websites for Additional Information
  1. National Cancer Institute (NCI). Cancer Types A-Z. Available at: http://www.cancer.gov/types. Accessed on April 5, 2018.
  2. National Cancer Institute (NCI). NCI Dictionary of Cancer Terms. Available at: http://www.cancer.gov/publications/dictionaries/cancer-terms. Accessed on April 5, 2018.
Index

Microtubule Inhibitor Agent

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

History

Status

Date

Action

Revised

05/03/2018

Medical Policy & Technology Assessment Committee (MPTAC) review.

Revised

05/02/2018

Hematology/Oncology Subcommittee review. Revised MN statements for use of protein-bound paclitaxel in recurrent, metastatic or high-risk uterine/endometrial cancer, removing statement A.; clarified MN criteria for Breast Cancer, NSCLC, and Ovarian Cancer, adding an “or” between MN statements A. and B.; and, clarified MN statement A. for Ovarian Cancer, moving criterion 1, “Used as a single agent,” into the body of the statement. Added MN statement VII. for use of protein-bound paclitaxel in the treatment of solid tumors where treatment with a taxane is medically appropriate and the individual has confirmed taxane (that is, solvent-based paclitaxel or docetaxel) hypersensitivity. Updated Coding, Discussion, References, and Websites for Additional Information sections.

Revised

01/25/2018

MPTAC review.

Revised

01/17/2018

Hematology/Oncology Subcommittee review. Added MN criteria for single agent use of protein-bound paclitaxel in uterine/endometrial cancer when criteria are met. Updated Discussion, Coding, References, and Websites for Additional Information sections. On 01/23/2018, approved revision to MN statements (B.) for use of protein-bound paclitaxel in the treatment of specific cancers (that is, sections I. B., any breast cancer; III. B., NSCLC; and IV. B., persistent or recurrent ovarian cancer) in an individual with confirmed taxane (that is, solvent-based paclitaxel or docetaxel) hypersensitivity. Added MN statement B. to criteria VI. for use of protein-bound paclitaxel in the treatment of recurrent, metastatic, or high-risk endometrial cancer in an individual with confirmed taxane (that is, solvent-based paclitaxel or docetaxel) hypersensitivity.

Revised

11/02/2017

MPTAC review.

Revised

11/01/2017

Hematology/Oncology Subcommittee review. The document header wording updated from “Current Effective Date” to “Publish Date.” Revised MN statement for use of protein-bound paclitaxel in persistent or recurrent ovarian cancer, adding criterion for use in combination with carboplatin in a platinum-sensitive individual with confirmed taxane (that is, solvent-based paclitaxel or docetaxel) hypersensitivity. Updated Discussion, Definitions, References, and Websites for Additional Information sections.

Reviewed

05/04/2017

MPTAC review.

Reviewed

05/03/2017

Hematology/Oncology Subcommittee review. Updated formatting in Clinical Indications section. Added “or docetaxel” to the MN statement for when protein-bound paclitaxel may be used as a substitute in the treatment of any breast cancer secondary to documented allergic reaction to docetaxel. Added a MN statement for use of protein-bound paclitaxel in the treatment of NSCLC when used as a substitute for either solvent-based paclitaxel or docetaxel when criteria are met. Updated Discussion, Definitions, References, and Websites for Additional Information sections.

New

05/05/2016

MPTAC review.

New

05/04/2016

Hematology/Oncology Subcommittee review. Initial document development.