JEVTANA (CABAZITAXEL) po DX - badanie kliniczne TROPIC

JEVTANA (CABAZITAXEL) po DX - badanie kliniczne TROPIC

Nieprzeczytany postautor: zosia bluszcz » 02 wrz 2019, 23:24

TROPIC Clinical Trial Design for JEVTANA® (cabazitaxel) Injection

JEVTANA Was Validated as a Second-line Treatment After Docetaxel in the TROPIC Trial

JEVTANA is a NCCN designated Category 1 second-line therapy for mCRPC5




IMPORTANT SAFETY INFORMATION
WARNING: NEUTROPENIA AND HYPERSENSITIVITY

Neutropenic deaths have been reported. Obtain frequent blood counts to monitor for neutropenia.
JEVTANA is contraindicated in patients with neutrophil counts of ≤1,500 cells/mm3. Primary prophylaxis with G-CSF is recommended in patients with high-risk clinical features.
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 is contraindicated in patients who have a history of severe hypersensitivity reactions to cabazitaxel or to other drugs formulated with polysorbate 80.

CONTRAINDICATIONS
JEVTANA is contraindicated in patients with neutrophil counts of ≤1,500/mm3, patients with a history of severe hypersensitivity reactions to cabazitaxel or to other drugs formulated with polysorbate 80, patients with severe hepatic impairment (total bilirubin >3x upper limit of normal (ULN)), and in pregnant women (JEVTANA can cause fetal harm and potential loss of pregnancy).

WARNINGS AND PRECAUTIONS
Bone Marrow Suppression (BMS): BMS 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 modification is needed. Primary prophylaxis with G-CSF is recommended in patients with high-risk clinical features. 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. Caution is recommended in patients with hemoglobin <10 g/dl.
Increased Toxicities in Elderly Patients: 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.

Hypersensitivity Reactions: Severe hypersensitivity reactions can occur. Premedicate all patients with antihistamines, corticosteroids and H2antagonists prior to JEVTANA. Observe patients closely, especially during the first and second infusions. Discontinue JEVTANA immediately if severe hypersensitivity occurs and treat as indicated.
Gastrointestinal (GI) Adverse Reactions: Nausea, vomiting and severe diarrhea may occur. Death related to diarrhea and electrolyte imbalance occurred in the clinical trial and mortality related to diarrhea has been reported. Intensive measures may be required for severe diarrhea and electrolyte imbalance. Rehydrate and treat with antiemetics and antidiarrheals as needed. If experiencing grade ≥3 diarrhea, dosage should be modified.
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, antiplatelet therapy or anticoagulants, 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: Cases, including those with fatal outcomes, have been reported. Identify cause and manage aggressively.
Urinary Disorders including Cystitis: Cystitis, radiation cystitis, and hematuria, including that requiring hospitalization, has been reported with JEVTANA in patients who previously received pelvic radiation. Cystitis from radiation recall may occur late in treatment with JEVTANA. Monitor patients who previously received pelvic radiation for signs and symptoms of cystitis while on JEVTANA. Interrupt or discontinue JEVTANA 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 have been reported and may be associated with fatal outcome. Patients with underlying lung disease may be at higher risk for these events. Acute respiratory distress syndrome may occur in the setting of infection. Interrupt JEVTANA if new or worsening pulmonary symptoms develop. Closely monitor, promptly investigate, and appropriately treat patients receiving JEVTANA. Consider discontinuation. The benefit of resuming JEVTANA treatment must be carefully evaluated.
Use in Patients with Hepatic Impairment: JEVTANA dose should be reduced for patients with mild (total bilirubin >1 to ≤1.5 x ULN or AST >1.5 x ULN) and moderate (total bilirubin >1.5 to ≤3.0 x ULN and any AST) hepatic impairment, based on tolerability data in these patients. Administer JEVTANA 20 mg/m2 for mild hepatic impairment. Administer JEVTANA 15 mg/m2 for moderate hepatic impairment. Monitor closely.


ADVERSE REACTIONS (ARs)
Deaths due to causes other than disease progression within 30 days of last JEVTANA dose were reported in 22 (3.8%) patients in the 20 mg/m2arm and 32 (5.4%) patients in the 25 mg/m2 arm. The most common fatal ARs were related to infections, and these occurred more commonly with 25 mg/m2 (n=15) vs. 20 mg/m2 (n=8).
The most common 1-4 grade ARs and laboratory abnormalities (≥10%) with JEVTANA 20 mg/m2 or 25 mg/m2 were neutropenia, anemia, leukopenia, thrombocytopenia, diarrhea, fatigue, nausea, vomiting, constipation, asthenia, abdominal pain, hematuria, back pain, and anorexia.
Grade 3-4 ARs occurring ≥5% more commonly with 25 mg/m2 versus 20 mg/m2 were leukopenia, neutropenia, and febrile neutropenia.

https://www.jevtanapro.com/trial-design/tropic
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FUJI study: Follow-Up of Jevtana® in real lIfe

Nieprzeczytany postautor: zosia bluszcz » 02 wrz 2019, 23:33

FUJI study: Follow-Up of Jevtana® in real lIfe
“French retrospective and protective multicenter observational study describing the survival, safety and quality of life of patients treated by cabazitaxel according to previous treatment lines in real-life setting”


FUJI study- Follow-Up of Jevtana® in real lIfe.pdf







ASCO 2018: Cabazitaxel in mCRPC: Real-life Use, Effectiveness, Safety, and Quality of Life in the FUJI Cohort


Chicago, IL (UroToday.com) Cabazitaxel is a novel tubulin-binding taxane drug with anti-tumor activity in docetaxel-resistant cancers. The seminal trial assessing cabazitaxel in mCRPC was the phase III TROPIC randomized controlled trial published in 2010 [1].
For TROPIC, 755 men with mCRPC with disease progression after docetaxel therapy were treated with 10 mg oral prednisone daily and randomized 1:1 to either 12 mg/m2 mitoxantrone IV or 25 mg/m2 cabazitaxel IV every three weeks. The primary endpoint was overall survival (OS) and PFS was a secondary endpoint. The median OS was 15.1 months (95%CI 14.1-16.3) in the cabazitaxel group and 12.7 months (11.6-13.7) in the mitoxantrone group (HR 0.70, 95%CI 0.59-0.83). Median PFS was 2.8 months (95%CI 2.4-3.0) in the cabazitaxel group and 1.4 months (95%CI 1.4-1.7) in the mitoxantrone group (HR 0.74, 95%CI 0.64-0.86). Cabazitaxel was first available in March 2012 in France, and the FUJI study is a post-authorization study of the real-life performance of cabazitaxel. At the ASCO 2018 annual meeting, Stephane Oudard, MD, PhD, presented real-life use, effectiveness, safety, and quality of life (QoL) for patients using cabazitaxel in the FUJI cohort.

FUJI is a French multi-center (42 centers) cohort study describing OS, safety, QoL (using FACT-P) and pain (using BPI-SF) among patients with mCRPC treated with cabazitaxel in a real-world setting.
From September 2013 to August 2015 patients were identified retrospectively (median follow-up 18 months), and from March 2016 to March 2017 patients were enrolled prospectively (median follow-up 6 months). For the retrospective cohort, OS was the primary outcome and predictors of OS were assessed using a multivariable Cox proportional hazards model. Safety outcomes were also assessed in the retrospective cohort.
The retrospective cohort of FUJI included 401 patients with a median age of 70 years comprising with cabazitaxel use in the second line setting (18%), third line setting (39%), fourth line setting (23%), or > fourth line setting (20%), with a median cabazitaxel use of 3.4 months. Treatment before cabazitaxel included docetaxel (100%), abiraterone acetate (77%), and enzalutamide (33%). The median OS was 11.9 months [95%CI 10.1-12.9]:

In multivariable analyses, factors associated with a shorter OS were:
Grade ≥ 3 adverse events: HR 2.05, 95%CI 1.53-2.73
Visceral metastases: HR 1.98, 95%CI 1.40-2.80
Polymedication > 5 drugs: HR 1.74, 95%CI 1.23-2.45
> 5 bone metastases: HR 1.74, 95%CI 1.20-2.53
Disease progression during docetaxel: HR 1.69, 95%CI 1.13-2.53
Disease progression within 3 months of last docetaxel cycle: HR 1.51, 95%CI 1.07-2.14
≥3 drugs such as docetaxel, abiraterone acetate, enzalutamide before cabazitaxel: HR 1.39, 95%CI 1.00-1.92
PSA ≥ 135 ng/ml: HR 1.36, 95%CI 1.01-1.82

Factors associated with better OS were:
≥ 10-yr cancer history before cabazitaxel: HR 0.66, 95%CI 0.46-0.96
≥ 6 months from last docetaxel dose to cabazitaxel initiation: HR 0.71 95%CI 0.52-0.97

Grade ≥ 3 AEs occurred in 55% of patients receiving cabazitaxel, including anemia (27%), neutropenia (15%), febrile neutropenia (8%), renal failure (7%), and septic shock (5%).

The prospective cohort of FUJI included 61 patients with a median age of 72 years, previously treated with docetaxel (98%), abiraterone acetate (61%) and enzalutamide (61%). Among 49 patients evaluable for QoL, 41% of patients experienced improved QoL, 29% maintained, and 38% deteriorated using cabazitaxel. Among 44 evaluable for pain assessment, 25% had pain decrease ≥ 1 level, 50% were stable and 25% increase ≥ 1 level.

Considering that many patients with advanced malignancies will not qualify for enrollment in clinical trials, it is important for real-world studies to review their outcomes when drugs are used outside of clinical trials. Although the median OS for patients receiving cabazitaxel as part of the FUJI cohort was lower than those in TROPIC (11.9 vs 15.1 months [1]), very few FUJI patients would have satisfied TROPIC inclusion criteria. Importantly, despite not satisfying TROPIC inclusion criteria, there were no new safety issues reported.


Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre,
https://www.urotoday.com/conference-hig ... ohort.html
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