SANOFI ONCOLOGY
JEVTANA® (cabazitaxel) Injection

TROPIC: Landmark Phase III Trial
in Second-line mHRPC

Key details about the trial include1,2

  • Large, international, randomized, open-label registration study
  • Enrolled patients with mHRPC who progressed on or after docetaxel
  • Conducted at 146 sites in 26 countries
  • Controlled versus an active agent: mitoxantrone

Study Design

Endpoints1

  • Primary endpoint: Overall survival
  • Secondary endpoints: Investigator-assessed tumor response,* safety, pharmacokinetics

Eligibility criteria for participation in the trial included1

  • >18 years of age
  • mHRPC either measurable by RECIST criteria or nonmeasurable disease with rising PSA levels or appearance of new lesions
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2
  • Neutrophils >1,500 cells/mm3, platelets >>100,000 cells/mm3, hemoglobin >10 g/dL, creatinine <1.5 x upper limit of normal (ULN), total bilirubin <1 x ULN, AST <1.5 x ULN, and ALT <1.5 x ULN
  • Patients with a history of congestive heart failure or myocardial infarction within the last 6 months, or patients with uncontrolled cardiac arrhythmias, angina pectoris, and/or hypertension, were not included in the study

Important Safety Information for JEVTANA®1

  • Patients ≥65 years of age were more likely to experience fatal outcomes not related to disease progression and certain adverse reactions, including neutropenia and febrile neutropenia. Monitor closely
  • Deaths due to causes other than disease progression within 30 days of last study drug dose were reported in 18 (5%) JEVTANA®-treated patients and 3 (<1%) mitoxantrone-treated patients
  • The most common fatal adverse reactions in JEVTANA®-treated patients were infections (n=5) and renal failure (n=4)
  • The majority (4 of 5 patients) of fatal infection-related adverse reactions occurred after a single dose of JEVTANA®. Other fatal adverse reactions in JEVTANA®-treated patients included ventricular fibrillation, cerebral hemorrhage, and dyspnea

Important Safety Information for JEVTANA® (cabazitaxel) Injection

WARNING: NEUTROPENIA AND HYPERSENSITIVITY

  • Neutropenic deaths have been reported. In order to monitor the occurrence of neutropenia, frequent blood cell counts should be performed on all patients receiving JEVTANA®. JEVTANA® should not be given to patients with neutrophil counts of ≤1,500 cells/mm3
  • Severe hypersensitivity reactions can occur and may include generalized rash/erythema, hypotension and bronchospasm. Severe hypersensitivity reactions require immediate discontinuation of the JEVTANA® infusion and administration of appropriate therapy. Patients should receive premedication
  • JEVTANA® must not be given to patients who have a history of severe hypersensitivity reactions to JEVTANA® or to other drugs formulated with polysorbate 80

CONTRAINDICATIONS

  • JEVTANA® should not be used in patients with neutrophil counts of ≤1,500/mm3
  • JEVTANA® is contraindicated in patients who have a history of severe hypersensitivity reactions to JEVTANA® or to other drugs formulated with polysorbate 80

WARNINGS AND PRECAUTIONS

  • Neutropenic deaths have been reported
    • 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
    • Monitor blood counts frequently to determine if initiation of G-CSF and/or dosage modification is needed
    • Primary prophylaxis with G-CSF should be considered in patients with high-risk clinical features
  • Severe hypersensitivity reactions can occur
    • Premedicate with antihistamines, corticosteroids and H2 antagonists
    • Patients should be observed closely for hypersensitivity reactions, especially during the first and second infusions
    • Discontinue infusion immediately if hypersensitivity is observed and treat as indicated
  • Mortality related to diarrhea has been reported
    • Rehydrate and treat with anti-emetics and anti-diarrheals as needed
    • If experiencing grade ≥3 diarrhea, dosage should be modified
  • Nausea, vomiting and severe diarrhea, at times, may occur. Death related to diarrhea and electrolyte imbalance occurred in the randomized clinical trial. Intensive measures may be required for severe diarrhea and electrolyte imbalance
  • Gastrointestinal (GI) hemorrhage and perforation, ileus, enterocolitis, neutropenic enterocolitis, including fatal outcome, have been reported
    • Risk may be increased with neutropenia, age, steroid use, concomitant use of NSAIDs, anti-platelet therapy or anti-coagulants, and prior history of pelvic radiotherapy, adhesions, ulceration and GI bleeding
    • Abdominal pain and tenderness, fever, persistent constipation, diarrhea, with or without neutropenia, may be early manifestations of serious GI toxicity and should be evaluated and treated promptly
    • JEVTANA® treatment delay or discontinuation may be necessary
  • Renal failure, including cases with fatal outcomes, has been reported. Identify cause and manage aggressively
  • Patients ≥65 years of age were more likely to experience fatal outcomes not related to disease progression and certain adverse reactions, including neutropenia and febrile neutropenia. Monitor closely
  • Patients with impaired hepatic function were excluded from the randomized clinical trial
    • Hepatic impairment is likely to increase the JEVTANA® concentrations
    • JEVTANA® should not be given to patients with hepatic impairment
  • JEVTANA® can cause fetal harm when administered to a pregnant woman
    • There are no adequate and well-controlled studies in pregnant women using JEVTANA®
    • Women of childbearing potential should be advised to avoid becoming pregnant during treatment with JEVTANA®

ADVERSE REACTIONS

  • Deaths due to causes other than disease progression within 30 days of last study drug dose were reported in 18 (5%) JEVTANA®-treated patients. The most common fatal adverse reactions in JEVTANA®-treated patients were infections (n=5) and renal failure (n=4)
  • The most common (≥10%) grade 1-4 adverse reactions were anemia, leukopenia, neutropenia, thrombocytopenia, diarrhea, fatigue, nausea, vomiting, constipation, asthenia, abdominal pain, hematuria, back pain, anorexia, peripheral neuropathy, pyrexia, dyspnea, dysgeusia, cough, arthralgia, and alopecia
  • The most common (≥5%) grade 3-4 adverse reactions in patients who received JEVTANA® were neutropenia, leukopenia, anemia, febrile neutropenia, diarrhea, fatigue, and asthenia

Please see full prescribing information including boxed WARNING.

* For measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST).
mHRPC=hormone-refractory metastatic prostate cancer; PSA=prostate-specific antigen.

References
1. JEVTANA® Prescribing Information. Bridgewater, NJ: sanofi-aventis U.S. LLC; March 2014. 2. de Bono JS, Oudard S, Ozguroglu M, et al; for the TROPIC Investigators. 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.

Important Safety Information
for JEVTANA® (cabazitaxel) Injection


WARNING: NEUTROPENIA AND HYPERSENSITIVITY

  • Neutropenic deaths have been reported. In order to monitor the occurrence of neutropenia, frequent blood cell counts should be performed on all patients receiving JEVTANA®. JEVTANA® should not be given to patients with neutrophil counts of ≤1,500 cells/mm3
  • Severe hypersensitivity reactions can occur and may include generalized rash/erythema, hypotension and bronchospasm. Severe hypersensitivity reactions require immediate discontinuation of the JEVTANA® infusion and administration of appropriate therapy. Patients should receive premedication
  • JEVTANA® must not be given to patients who have a history of severe hypersensitivity reactions to JEVTANA® or to other drugs formulated with polysorbate 80
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JEVTANA® is a microtubule inhibitor indicated in combination with prednisone for the treatment of patients with hormone-refractory metastatic prostate cancer (mHRPC) previously treated with a docetaxel-containing treatment regimen.