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Date Printed: June 26, 2017: 11:44 AM

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09-J1000-77

Original Effective Date: 12/15/12

Reviewed: 03/08/17

Revised: 04/15/17

Subject: Cabazitaxel (Jevtana®) Injection

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           

Dosage/Administration

Position Statement

Billing/Coding

Reimbursement

Program Exceptions

Definitions

           

Related Guidelines

Other

References

Updates

 
           

DESCRIPTION:

Cabazitaxel (Jevtana®) is a novel semi-synthetic taxane demonstrating in vitro activity in docetaxel-sensitive and docetaxel-resistant cell lines and tumor models. Similar to other taxanes (e.g., paclitaxel [Taxol®], docetaxel [(Taxotere®]), cabazitaxel impairs microtubule assembly ultimately resulting in mitotic arrest and apoptosis. Although cabazitaxel is mechanistically similar to paclitaxel and docetaxel, it has poor affinity for P-glycoprotein (P-gp); consequently, cabazitaxel’s penetration of the blood-brain barrier is superior to that of paclitaxel and docetaxel.

Cabazitaxel was approved by the Food and Drug Administration (FDA) in June 2010, for the treatment of individuals with hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen. For most men with metastatic prostate cancer, androgen-deprivation therapy, usually with a luteinizing hormone-releasing hormone (LHRH) agonist, improves symptoms, but tumors invariably become castration resistant and progressive disease ensues. No consensus exists for the best additional therapy following docetaxel therapy in metastatic castration-recurrent prostate cancer (CRPC) individuals. Options listed by the National Comprehensive Cancer Network (NCCN) include abiraterone acetate (Zytiga®) with prednisone, cabazitaxel with prednisone, radium R-223 (Xofigo®) (if no visceral metastases and symptomatic bone metastases), docetaxel re-challenge, mitoxantrone with prednisone, secondary hormone therapy, sipuleucel-T (Provenge®) (if certain criteria are met), best supportive care, and participation in clinical trials. The NCCN states that all patients with metastatic CRPC should maintain castrate levels of serum testosterone (<50 ng/dL) and received best supportive care.

Although NCCN’s inclusion of cabazitaxel as an option for second-line therapy is a category 1 recommendation based on randomized phase III study data, the extension of survival is relatively short and the side effects are relatively high. Careful monitoring (e.g., neutrophil counts), prophylactic granulocyte colony-stimulating factor (G-CSF), and supportive care (e.g., pre-medication with antihistamines, corticosteroids, histamine-2 receptor antagonists, anti-emetics, and anti-diarrheals) are important components of cabazitaxel administration.

POSITION STATEMENT:

The use of cabazitaxel (Jevtana®) meets the definition of medical necessity when ALL of the following criteria are met:

1. Member is diagnosed with metastatic, castration-recurrent prostate cancer (CRPC, a.k.a., castration-resistant or hormone-refractory prostate cancer) - lab documentation of a recent (past 90 days) serum testosterone level at castrate level (<50 ng/dL) must be submitted for members receiving medical castration. A chart note documenting a bilateral orchiectomy must be submitted for members who have received surgical castration.

2. Member has previously received a docetaxel-containing regimen for treatment of their CRPC

3. Cabazitaxel is used in combination with prednisone

4. Member has a neutrophil count of greater than 1,500 cells/mm3

5. Member does NOT have severe hepatic impairment [total bilirubin >3-times the upper limit of normal (ULN)]

6. Dosage of cabazitaxel does not exceed 25 mg/m2 every 3 weeks (i.e., 25 mg/m2 once per cycle)

7. No more than 10 total cycles (10 doses) of treatment with cabazitaxel will be given

8. Cabazitaxel is not used concomitantly with ANY of the following:

a. Abiraterone (Zytiga®)

b. Docetaxel (Taxotere®)

c. Enzalutamide (Xtandi®)

d. Mitoxantrone (Novantrone®)

e. Radium-223 (Xofigo®)

f. Sipuleucel-T (Provenge®)

Approval duration: 36 weeks and not to exceed 10 total cycles (10 doses) of treatment

DOSAGE/ADMINISTRATION:

THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER’S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE.

FDA-approved: Cabazitaxel is, in combination with prednisone, for the treatment of members with hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing treatment regimen. The recommended dosage is based on calculation of Body Surface Area (BSA) and is 25 mg/m2 every three weeks with oral prednisone 10 mg daily throughout treatment. Cabazitaxel is administered as an intravenous (IV) infusion over one hour. PVC equipment should not be used.

Pre-medication, consisting of an antihistamine (e.g., diphenhydramine 25 mg), corticosteroid (e.g., dexamethasone 8 mg), and a histamine-2 receptor antagonist (e.g., ranitidine 50 mg) should be administered 30 minutes prior to each cabazitaxel dose. Antiemetic prophylaxis, either oral or intravenous, is also recommended as needed.

Dosage Adjustments

Renal Impairment: No dose adjustment is necessary in patients with renal impairment not requiring hemodialysis. Patients presenting with end-stage renal disease (creatinine clearance < 5 mL/min/1.73m2), should be monitored carefully during treatment.

Hepatic Impairment:

o Mild hepatic impairment (total bilirubin >1 to ≤1.5 × Upper Limit of Normal (ULN) or AST >1.5 × ULN): Reduce starting dose to 20 mg/m2.

o Moderate hepatic impairment (total bilirubin >1.5 to ≤3 × ULN and AST = any): Reduce starting dose to 15 mg/m2 based on tolerability data in these patients; however, the efficacy of this dose is unknown.

o Severe hepatic impairment (total bilirubin > 3 × ULN): Cabazitaxel is contraindicated in patients with severe hepatic impairment.

Strong CYP3A Inhibitors: Concomitant drugs that are strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) may increase plasma concentrations of cabazitaxel. Avoid the coadministration with these drugs. If patients require co-administration of a strong CYP3A inhibitor, consider a 25% dose reduction of cabazitaxel.

Adverse reactions: the dose of cabazitaxel should be reduced to 20 mg/m2 if members experience the adverse reactions described in Table 1. If the member continues to experience any of these reactions at the 20 mg/m2 dose, cabazitaxel should be discontinued.

Table 1

Recommended Dosage Adjustments for Adverse Reactions

Toxicity

Dosage Modification

Prolonged grade 3 or greater neutropenia (greater than 1 week) despite appropriate medication including G-CSF

Delay treatment until neutrophil count is greater than1,500 cells/mm3, then reduce dose to 20 mg/m2. Use G-CSF for secondary prophylaxis.

Febrile neutropenia or neutropenic infection

Delay treatment until improvement or resolution, and until neutrophil count is greater than 1,500 cells/mm3, then reduce dose to 20 mg/m2. Use G-CSF for secondary prophylaxis

Grade 3 or greater diarrhea or persisting diarrhea despite appropriate medication, fluid and electrolytes replacement.

Delay treatment until improvement or resolution, then reduce dose to 20 mg/m2.

Grade 2 peripheral neuropathy

Delay treatment until improvement or resolution, then reduce dose to 20 mg/m2.

Grade ≥3 peripheral neuropathy

Discontinue cabazitaxel treatment

G-CSF = Granulocyte Colony Stimulating Factor

Drug Availability

Cabazitaxel is available as a 60 mg/1.5 mL injection kit consisting of the following:

• Cabazitaxel injection: 60 mg cabazitaxel in 1.5 mL polysorbate 80

• Diluent: 5.7 mL of 13% (w/w) ethanol in water for injection

PRECAUTIONS:

CONTRAINDICATIONS

• Neutrophil counts of ≤1,500/mm3

• History of severe hypersensitivity reactions to cabazitaxel or to other drugs formulated with polysorbate 80

• Severe hepatic impairment (total bilirubin >3 × ULN)

BOXED WARNING

Neutropenia: Neutropenic deaths have been reported. Frequent blood counts should be obtained to monitor for neutropenia. Cabazitaxel is contraindicated in members with neutrophil counts less than or equal to 1,500 cells/mm3.

Severe hypersensitivity: Severe hypersensitivity can occur and may include generalized rash/erythema, hypotension and bronchospasm. If severe reactions occur, discontinue cabazitaxel and administer appropriate therapy. Cabazitaxel is contraindicated in members with a history of severe hypersensitivity reactions to cabazitaxel or other drugs formulated with polysorbate 80.

WARNINGS AND PRECAUTIONS

Bone Marrow Suppression: Bone marrow suppression manifested as neutropenia, anemia, thrombocytopenia and/or pancytopenia may occur. Neutropenic deaths have been reported. Monitor blood counts frequently to determine if initiation of G-CSF and/or dosage adjustment is needed. Primary prophylaxis with G-CSF should be considered in members with high-risk clinical features (e.g., age greater than 65, poor performance status, previous episodes of febrile neutropenia, other serious comorbidities, etc.). See table 1 for dosage adjustment information.

Hypersensitivity Reactions: Pre-medicate members with an antihistamine, corticosteroid, and histamine-2 receptor antagonist at least 30 minutes prior to each dose of cabazitaxel.

Gastrointestinal Adverse Reactions (nausea, vomiting, diarrhea): Mortality related to diarrhea has been reported. Members should be rehydrated and antiemetics and anti-diarrheals should be administered as needed. If member is experiencing grade ≥ 3 diarrhea, the dosage should be adjusted (refer to Table 1).

Renal Failure: Renal failure, including cases with fatal outcomes, has been reported. The cause should be identified and managed aggressively.

Respiratory disorders: Interstitial pneumonia/pneumonitis, interstitial lung disease and acute respiratory distress syndrome, including fatal outcomes, have been reported. Patients with underlying lung disease may be at higher risk for these events. Interrupt treatment if new or worsening pulmonary symptoms develop.

Geriatric Population: In clinical trials, individuals 65 years of age or older were more likely to experience fatal outcomes not related to disease progression and certain adverse reactions, including neutropenia and febrile neutropenia. Members 65 years of age and older should be monitored closely.

Hepatic Impairment: Cabazitaxel is contraindicated in patients with severe hepatic impairment (total bilirubin > 3 × ULN). Dose should be reduced for patients with mild and moderate impairment, based on tolerability data in these patients. Administration of cabazitaxel to patients with mild and moderate hepatic impairment should be undertaken with caution and close monitoring of safety.

Pregnancy/Lactation

• Cabazitaxel is not indicated for use in female patients and can cause fetal harm when administered to a pregnant woman. Although there are no adequate and well-controlled studies evaluating cabazitaxel in pregnant women, non-clinical studies in animals have shown that cabazitaxel is embryotoxic, fetotoxic, and abortifacient.

• Cabazitaxel or cabazitaxel metabolites are excreted in maternal milk of lactating rats. While it is not known whether cabazitaxel is excreted in human milk, it may be prudent to avoid use in nursing women.

BILLING/CODING INFORMATION:

HCPCS Coding

J9043

Injection, cabazitaxel, 1 mg

ICD-10 Diagnoses Codes That Support Medical Necessity

C61

Malignant neoplasm of prostate

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Advantage Products: No National Coverage Determination (NCD) and/or Local Coverage Determination (LCD) were found at the time of the last guideline review date.

Medicare Part D: Not applicable.

DEFINITIONS:

Metastatic cancer: when cancer spreads from the primary site (place where it started) to other places in the body.

Castrate-resistant/recurrent prostate cancer (CRPC): disease progression despite androgen deprivation therapy (ADT) with either medication or surgery (i.e., removal/destruction of testicles), and may present as either a continuous rise in serum prostate-specific antigen (PSA) levels, the progression of pre-existing disease, and/or the appearance of new metastases.

RELATED GUIDELINES:

Abiraterone acetate (Zytiga™), 09-J1000-36
Cryosurgical Ablation of the Prostate (CSAP), 02-54000-14

Docetaxel (Taxotere®) IV, 09-J0000-95

Enzalutamide (Xtandi®) Capsules, 09-J1000-85

Gonadotropin Releasing Hormone Analogs and Antagonists, 09-J0000-48

Granulocyte Colony Stimulating Factors, 09-J0000-62

Paclitaxel and Nab-Paclitaxel IV, 09-J1000-05

Radium Ra 223 (Xofigo®) Injection, 09-J2000-01

OTHER:

None.

REFERENCES:

  1. Bahl A, Oudard S, Tombal B, et al. Impact of cabazitaxel on 2-year survival and palliation of tumour-related pain in men with metastatic castration-resistant prostate cancer treated in the TROPIC trial. Ann Oncol. 2013 Sep;24(9):2402-8. Epub 2013 May 30.
  2. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2017. Available at: www.clinicalpharmacilogy-ip.com. Accessed 2/17/17.
  3. de Bono JS, Oudard S, Ozguroglu M, TROPIC Investigators, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomized open-label trial. Lancet. 2010;376(9747):1147-54.
  4. Jevtana (cabazitaxel) [package insert]. Sanofi-Aventis U.S. LLC. Bridgewater (NJ): October 2016.
  5. Micromedex® Healthcare Series [Internet Database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed 2/17/17.
  6. National Comprehensive Cancer Network. Cancer Guidelines. Cancer Guidelines and Drugs and Biologics Compendium. Accessed 2/17/17.
  7. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Version 1.2017. Prostate Cancer. Available at: http://www.nccn.org/professionals/physician_gls/PDF/prostate.pdf. Accessed 2/20/17.
  8. Pal SK, Twardowski P, Sartor O. Critical appraisal of cabazitaxel in the management of advanced prostate cancer. Clin Interv Aging. 2010;5:395-402.
  9. Tannock IF, de Wit R, Berry WR, TAX 327 Investigators, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351(15):1502-15.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 03/08/17.

GUIDELINE UPDATE INFORMATION:

12/15/12

New Medical Coverage Guideline.

04/01/13

Review and revision to guideline; consisting of revising position statement, updating references and adding related guidelines.

04/15/14

Review and revision to guideline; consisting of revising position statement, updating references and program exceptions.

04/15/15

Review and revision to guideline; consisting of description, position statement, related guidelines, and updating of references.

12/15/15

Revision to guideline consisting of updating the position statement.

04/15/16

Review and revision to guideline consisting of updating the description section, position statement, dosage/administration, and references.

04/15/17

Review and revision to guideline consisting of updating the description section, position statement, and references. The total number of treatment cycles must not exceed ten and members must not have severe hepatic dysfunction or neutropenia (both contraindications),

Date Printed: June 26, 2017: 11:44 AM