Cabazitaxel (Jevtana®) for Patients with Metastatic Castration-Resistant Prostate Cancer

Written by: Alyson Leonard, PharmD, BCPS, BCOP Cone Health
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Cabazitaxel is indicated for treatment of patients with metastatic castration-resistant prostate (mCRPC) cancer previously treated with a docetaxel-containing treatment regimen in combination with prednisone.¹ The purpose of this PQI is to provide guidance for initiating cabazitaxel.

Background: Cabazitaxel was FDA approved in 2010 based on information from the phase 3 trial TROPIC that compared cabazitaxel plus prednisone to mitoxantrone in patients with mCRPC previously treated with a docetaxel-based treatment.² The recommended dose of cabazitaxel is now 20mg/m² every 3 weeks, the higher dose of 25mg/m² can be used at provider discretion for select patients.^1,3

The CARD trial evaluated the use of cabazitaxel with prednisone/prednisolone and G-CSF for patients with mCRPC previously treated with docetaxel and an androgen- signaling -targeted inhibitor (abiraterone or enzalutamide) who had progressed within 12 months. The study compared cabazitaxel to initiation of another androgen- signaling -targeted inhibitor not previously used. The median radiographic progression-free survival was 8 months with cabazitaxel + prednisone/prednisolone + G-CSF and 3.7 months with abiraterone + prednisone/prednisolone or enzalutamide (HR 0.54, p<0.0001). When comparing median overall survival, cabazitaxel had a longer overall survival compared to androgen-signaling-targeted inhibitor, 13.6 months vs 11 months. Overall, cabazitaxel was associated with a 36% risk of death reduction.  Secondary objectives of improvement in PFS, pain response, and time to symptomatic skeletal events favored cabazitaxel.^1,4

PQI Process:

• Review the medical record
  • Review past treatments for documentation of previous docetaxel administration
    • If docetaxel was not previously given, evaluate the reason for non-use. Per guidelines, patients who are not candidates for docetaxel can still be considered for cabazitaxel. (ex. pre-existing mild neuropathy prevented docetaxel use)⁵
  • Review labs for a recent CBC. Cabazitaxel is contraindicated in patients with neutrophil counts currently ≤1,500 cells/mm³.¹
• Review treatment plan: ¹
  • Verify pre-medication orders:
    • Antihistamine: diphenhydramine 25 mg or equivalent antihistamine
    • Corticosteroid: dexamethasone 8 mg or equivalent steroid
    • H2antagonist: famotidine 20 mg or equivalent H2 antagonist
  • Verify cabazitaxel dosing: 20 mg/m²administered every three weeks as a one-hour intravenous infusion
    • Dose adjustments needed for hepatic impairment; no adjustment necessary for renal impairment
  • If provider is starting dosing as 25 mg/m², strongly consider G-CSF and CINV prophylaxis, incidence of grade 3-4 nausea at this dose was 2% and grade 3-4 vomiting was 2%¹
  • Verify a prescription for prednisone has been entered

• Verify a prescription or order for antiemetic: prophylaxis recommended as needed (PO or IV)
• Evaluate the need for primary prophylaxis with G-CSF
  • Recommended for patient with high-risk clinical features such as previous episodes of febrile neutropenia, older patients, extensive prior radiation, poor performance or nutritional status, or other serious comorbidities
• Monitoring¹
  • CBC: baseline, weekly during cycle one, then before each treatment cycle
• Preparation¹
  • Cabazitaxel requires two dilutions for preparation
  • Mix cabazitaxel vial with the entire contents of the included 5.7 mL diluent vial
  • Withdraw the patient specific dose of cabazitaxel
  • Inject dose into a 250 mL PVC-free container of 0.9% sodium chloride (NS) or 5% dextrose (D5W)
    • If dose is >65 mg use a larger volume solution so the concentration is ≤0.26 mg/mL
  • Mix the final infusion solution by gently inverting the bag
• Administration¹
  • IV over hour with a 0.22-mcm nominal pore size inline filter

Patient Centered Activities:

• Patient Education
  • Review the risk of infusion reactions, with cabazitaxel they are most likely to occur during first or second infusion. Signs of a reaction may include rash/itching, feeling dizzy, chest or throat tightness, breathing problems, face swelling
  • Instruct patient to report any adverse events, such as fever, diarrhea, nausea/vomiting, numbness/tingling of the hands or feet, or fatigue
  • Ensure patient has access to supportive medications
    • Anti-nausea (ex. 5-HT3 receptor antagonist, metoclopramide, or prochlorperazine)
    • Anti-diarrheal (ex. loperamide)
  • Provide written information to patient on medication

Supplemental Information:

• CareASSIST Patient Support Program
  • Program can assist eligible patients with no insurance coverage or who lack coverage

*Medicare Part B patients with no supplemental insurance coverage may be eligible

• CareASSIST Copay Program
  • Available to commercial insurance patient to help decrease out of pocket cost

References:

1. Jevtana® (cabazitaxel) [prescribing information]. Bridgewater, NJ: Sanofi-Aventis U.S. LLC.
2. de Bono JS, Oudard S, Ozguroglu M, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010;376(9747):1147-1154.
3. 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;35(28):3198-3206.
4. de Wit R, de Bono J, Sternberg CN, et al. Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer. N Engl J Med. 2019;381(26):2506-2518.
5. National Comprehensive Cancer Network. Prostate Cancer. https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf.

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