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This medical policy (medical coverage guideline) is Copyright 2017, Blue Cross and Blue Shield of Florida (BCBSF). All Rights Reserved. You may not copy or use this document or disclose its contents without the express written permission of BCBSF. The medical codes referenced in this document may be proprietary and owned by others. BCBSF makes no claim of ownership of such codes. Our use of such codes in this document is for explanation and guidance and should not be construed as a license for their use by you. Before utilizing the codes, please be sure that to the extent required, you have secured any appropriate licenses for such use. Current Procedural Terminology (CPT) is copyright 2017 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values, or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use. CPT® is a trademark of the American Medical Association. 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.

09-J1000-77

Original Effective Date: 12/15/12

Reviewed: 03/14/18

Revised: 04/15/18

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) for patients with metastatic CRPC and prior docetaxel therapy include abiraterone acetate (Zytiga) with prednisone, enzalutamide (Xtandi), cabazitaxel with concurrent steroid (i.e., daily prednisone or dexamethasone on the day of chemotherapy), 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 following docetaxel 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. The NCCN encourages participation in clinical trials for these patients. If cabazitaxel is to be used, the NCCN states that selection of patients without neuropathy and with adequate liver, kidney, and bone marrow function is necessary given the high risk of neutropenia and other adverse effects. 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. The NCCN guidelines mention that CRPC patients who are not candidates for docetaxel, who are intolerant of docetaxel, or who have pre-existing mild peripheral neuropathy should be considered for treatment with cabazitaxel.

POSITION STATEMENT:

The use of cabazitaxel (Jevtana) meets the definition of medical necessity when ALL of the following criteria are met (“1” to “8”):

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. ANY of the following (“a”, “b”, or “c”):

a. Member has previously received a docetaxel-containing regimen for treatment of their prostate cancer and had progressive or relapsed disease

b. Member has previously received a docetaxel-containing regimen and had intolerable adverse effects that are expected to be less likely with cabazitaxel (e.g., peripheral neuropathy, fluid retention) – the specific adverse effect must be provided

c. Member is not a suitable candidate for docetaxel treatment due to pre-existing peripheral neuropathy

3. Cabazitaxel will be used in combination with either daily prednisone or dexamethasone given on the day of chemotherapy

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 indicated, in combination with prednisone, for the treatment of members with metastatic castration-resistant prostate cancer previously treated with a docetaxel-containing treatment regimen. The recommended dosage is based on calculation of Body Surface Area (BSA) and is 20 mg/m2 every three weeks with oral prednisone 10 mg daily throughout treatment. A dose of 25 mg/m2 can be used in select patients at the discretion of the treating healthcare provider. 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): Administer at a dose of 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 from 25 to 20 mg/m2 or from 20 to 15 mg/m2 if members experience the adverse reactions described in Table 1. If the member continues to experience any of these reactions at the 15 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 the doageby one dose level (i.e., by 5 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 the dosage by one dose level. 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 the dosage by one dose level.

Grade 2 peripheral neuropathy

Delay treatment until improvement or resolution, then reduce the dosage by one dose level.

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)

Pregnancy – can cause fetal harm and potential loss of pregnancy

BOXED WARNING

WARNING: NEUTROPENIA AND HYPERSENSITIVITY

Neutropenia: Neutropenic deaths have been reported. Monitor for neutropenia with frequent blood cell counts. Cabazitaxel is contraindicated in members with neutrophil counts less than or equal to 1,500 cells/mm3. Primary prophylaxis with G-CSF is recommended in patients with high-risk clinical features.

Severe hypersensitivity: Severe hypersensitivity can occur and may include generalized rash/erythema, hypotension and bronchospasm. Severe hypersensitivity reactions require immediate discontinuation of the cabazitaxel infusion and administration of appropriate therapy. Patients should receive premedication. Cabazitaxel is contraindicated in patients who have 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. Closely monitor patients with hemoglobin <10 g/dL. Based on guidelines for the use of G-CSF and the adverse reactions profile of cabazitaxel, primary prophylaxis with G-CSF is recommended in patients with high-risk clinical features (older patients, poor performance status, previous episodes of febrile neutropenia, extensive prior radiation ports, poor nutritional status, or other serious comorbidities) that predispose them to increased complications from prolonged neutropenia. The effectiveness of primary prophylaxis with G-CSF has not been studied. Therapeutic use of G-CSF and secondary prophylaxis should be considered in all patients at increased risk for neutropenia complications. Monitoring of complete blood counts is essential on a weekly basis during cycle 1 and before each treatment cycle thereafter so that the dose can be adjusted, if needed. See table 1 for dosage adjustment information.

Increased Toxicities in Elderly Patients: Patients ≥65 years of age are more likely to experience certain adverse reactions, including neutropenia and febrile neutropenia. The incidence of the following grade 3–4 adverse reactions were higher in patients ≥65 years of age compared to younger patients; neutropenia (87% vs 74%), and febrile neutropenia (8% vs 6%).

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). The incidence of gastrointestinal adverse reactions is greater in patients who have received prior radiation.

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

Urinary Disorders Including Cystitis: Cystitis, radiation cystitis, and hematuria, including that requiring hospitalization, has been reported with cabazitaxel in patients who previously received pelvic radiation. Cystitis from radiation recall may occur late in treatment with cabazitaxel. Monitor patients who previously received pelvic radiation for signs and symptoms of cystitis while on cabazitaxel. Interrupt or discontinue cabazitaxel in patients experiencing severe hemorrhagic cystitis. Medical and/or surgical supportive treatment may be required to treat severe hemorrhagic cystitis.

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.

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.

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:

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.; 2018. Available at: www.clinicalpharmacilogy-ip.com. Accessed 2/21/18.
  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. Eisenberger M, Hardy-Bessard AC, Kim CS, et al. Phase III Study Comparing a Reduced Dose of Cabazitaxel (20 mg/m2) and the Currently Approved Dose (25 mg/m2) in Postdocetaxel Patients With Metastatic Castration-Resistant Prostate Cancer-PROSELICA. J Clin Oncol. 2017 Oct 1;35(28):3198-3206. Epub 2017 Aug 15.
  5. Jevtana (cabazitaxel) [package insert]. Sanofi-Aventis U.S. LLC. Bridgewater (NJ): January 2018.
  6. Micromedex® Healthcare Series [Internet Database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed 2/21/18.
  7. National Comprehensive Cancer Network. Cancer Guidelines. Cancer Guidelines and Drugs and Biologics Compendium. Accessed 2/21/18.
  8. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Version 1.2018. Prostate Cancer. Available at: http://www.nccn.org/professionals/physician_gls/PDF/prostate.pdf. Accessed 2/21/18.
  9. Oudard S, Fizazi K, Sengeløv L, et al. Cabazitaxel Versus Docetaxel As First-Line Therapy for Patients With Metastatic Castration-Resistant Prostate Cancer: A Randomized Phase III Trial-FIRSTANA. J Clin Oncol. 2017 Oct 1;35(28):3189-3197. Epub 2017 Jul 28.
  10. Pal SK, Twardowski P, Sartor O. Critical appraisal of cabazitaxel in the management of advanced prostate cancer. Clin Interv Aging. 2010;5:395-402.
  11. 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 03/14/18.

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),

04/15/17

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

Date Printed: May 21, 2018: 08:30 PM