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Prescribing Information/Medication Guide  |  Important Safety Information
 
 
NOW WITH OVERALL
SURVIVAL DATA
 
   
  In patients with relapsed or refractory FLT3m+ AML,* XOSPATA demonstrated efficacy on the basis of CR/CRh, the duration of CR/CRh (DOR) and the rate of conversion from transfusion dependence to transfusion independence, as determined in the first interim analysis of the ADMIRAL trial. The efficacy of XOSPATA was confirmed with the assessment of overall survival (OS) at the final analysis § of the study.1  
 
In the final analysis, XOSPATA delivered superior overall survival vs salvage chemotherapy1:
vs salvage chemotherapy (n=124)
9.3 months median OS
  (95% CI: 7.7, 10.7) vs 5.6 months with salvage chemotherapy (95% CI: 4.7, 7.3)
HR=0.64 (95% CI: 0.49, 0.83); P=0.0004
 
In the first interim analysis, XOSPATA demonstrated1:
(95% CI: 14.5, 28.8; n=29/138)
 
 
WARNING: DIFFERENTIATION SYNDROME
Patients treated with XOSPATA have experienced symptoms of differentiation syndrome, which can be fatal or life-threatening if not treated. Symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, or renal dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.
 
  Indication  
  XOSPATA is indicated for the treatment of adult patients who have relapsed or refractory acute myeloid leukemia (AML) with a FMS-like tyrosine kinase 3 (FLT3) mutation as detected by an FDA-approved test.  
  Select Safety Information  
  Contraindications  
  XOSPATA is contraindicated in patients with hypersensitivity to gilteritinib or any of the excipients. Anaphylactic reactions have been observed in clinical trials.  
  Please see additional Important Safety Information below, including
BOXED WARNING.
 
 
 
     
   
  XOSPATA Delivered Superior Survival vs Salvage Chemotherapy in Relapsed or Refractory FLT3m+ AML1  
     
   
   
 
XOSPATA delivered superior survival with a median OS of 9.3 months (95% CI: 7.7, 10.7) vs 5.6 months with salvage chemotherapy (95% CI: 4.7, 7.3)1
XOSPATA more than doubled the 1-year survival rate compared with salvage chemotherapy2||
  37.1% with XOSPATA (95% CI: 30.7, 43.6)
  16.7% with salvage chemotherapy (95% CI: 9.9, 25.0)
In the exploratory subgroup analyses that evaluated survival according to whether patients were preselected for high-intensity chemotherapy or low-intensity chemotherapy1:
  XOSPATA reduced the risk of death by 34% vs high-intensity salvage chemotherapy (HR=0.66; 95% CI: 0.47, 0.93)
  XOSPATA reduced the risk of death by 44% vs low-intensity salvage chemotherapy (HR=0.56; 95% CI: 0.38, 0.84)
||Survival rate and 95% CI were estimated using the Kaplan-Meier method and the Greenwood formula.2
 
   
  Interim Analysis Endpoints Included Rate of CR/CRh, DOR and Rate of Conversion to Transfusion Independence1  
     
   
 
(95% CI: 14.5, 28.8; n=29/138)
   
(95% CI: 6.8, 18.1; n=16/138)
(95% CI: 5.1, 15.6; n=13/138)
 
 
 
Only responses prior to HSCT were included in the response rate
The median follow-up was 4.6 months (95% CI: 2.8, 15.8)
Among patients with FLT3-ITD or FLT3-ITD-TKD mutations, the rate of CR/CRh was 23% (n=29/126) and none of the 12 patients with FLT3-TKD only mutations achieved CR/CRh
In patients who achieved CR/CRh with XOSPATA (n=29/138), the median time to first response was 3.6 months (range: 0.9 to 9.6 months)
CR was defined as normal marrow differential with <5% blasts, ANC ≥1.0 × 109/L and platelets ≥100 × 109/L, no evidence of extramedullary leukemia and must have been RBC and platelet transfusion independent
CRh was defined as marrow blasts <5%, partial hematologic recovery, ANC ≥0.5 × 109/L and platelets ≥50 × 109/L, no evidence of extramedullary leukemia and could not have been classified as CR
 
   
 
4.6 months
median duration of CR/CRh
(range: 0.1 to 15.8; n=29/138)
8.6 months
median duration of CR
(range: 1.0 to 13.8; n=16/138)
2.9 months
median duration of CRh
(range: 0.1 to 15.8; n=13/138)
 
   
 
Among patients in the XOSPATA arm who were transfusion dependent at baseline, 31.1% became transfusion independent with XOSPATA during any 56-day post-baseline period (n=33/106)
Of the 32 patients in the XOSPATA arm who were transfusion independent at baseline, 53.1% remained transfusion independent during any 56-day post-baseline period (n=17/32)
Transfusion independence is defined as patients who were dependent on RBC and/or platelet transfusions at baseline and became independent of RBC and platelet transfusions during any 56-day post-baseline period
 
  Study Design  
 
XOSPATA was evaluated in a Phase 3, open-label, multicenter, randomized clinical trial compared with a prespecified salvage chemotherapy in 371 adult patients with relapsed or refractory FLT3m+ AML1,2
The efficacy of XOSPATA was based on an interim analysis and a final analysis1:
  The first interim analysis evaluated the endpoints of CR/CRh, DOR and the rate of conversion from transfusion dependence to transfusion independence in 138 patients treated with XOSPATA
  The final analysis evaluated the endpoint of OS and was measured from the date of randomization until death by any cause
 
 
Randomization was stratified by patient response to first-line AML treatment and prespecified chemotherapy1#
Prespecified chemotherapy regimens included1:
  High-intensity combination regimens MEC** and FLAG-IDA††
  Low-intensity regimens LDAC‡‡ and AZA§§
 
 
* FLT3 mutation status: FLT3-ITD, FLT3-TKD and FLT3-ITD-TKD.1
CR defined as normal marrow differential with <5% blasts, ANC ≥1.0 × 109/L and platelets ≥100 × 109/L, no evidence of extramedullary leukemia and must have been RBC and platelet transfusion independent.1
CRh defined as marrow blasts <5%, partial hematologic recovery, ANC ≥0.5 × 109/L and platelets ≥50 × 109/L, no evidence of extramedullary leukemia and could not have been classified as CR.1
§ The OS endpoint was measured from the date of randomization until death by any cause in the final analysis, which included 371 patients randomized 2:1 to receive XOSPATA or a prespecified salvage chemotherapy regimen.1
Response was ongoing.1
# Prior AML chemotherapy regimens included standard-dose cytarabine + idarubicin (39%); high-dose cytarabine (27%); standard-dose cytarabine + daunorubicin (26%); azacitidine (7%); decitabine (5%); high-dose cytarabine + daunorubicin (4%); low-dose cytarabine (4%); high-dose cytarabine + idarubicin (3%); standard-dose cytarabine + mitoxantrone (3%) and standard-dose cytarabine + daunorubicin + cladribine (1%); as well as other regimens (44%).2
** MEC: mitoxantrone 8 mg/m2, etoposide 100 mg/m2 and cytarabine 1000 mg/m2 once daily by IV infusion days 1 to 5.1
†† FLAG-IDA: granulocyte colony-stimulating factor 300 mcg/m2 once daily by SC injection days 1 to 5, fludarabine 30 mg/m2 once daily by IV infusion days 2 through 6, cytarabine 2000 mg/m2 once daily by IV infusion days 2 through 6, idarubicin 10 mg/monce daily by IV infusion days 2 through 4. 1
‡‡ LDAC: cytarabine 20 mg twice daily by SC injection or IV infusion for 10 days.1
§§ AZA: azacitidine 75 mg/m2 once daily by SC injection or IV infusion for 7 days.1
 
  AML, acute myeloid leukemia; ANC, absolute neutrophil count; CI, confidence interval; CR, complete remission; CRh, complete remission with partial hematologic response; DOR, duration of remission; FLT3, FMS-like tyrosine kinase 3; GPO, group purchasing organization; HR, hazard ratio; HSCT, hematopoietic stem cell transplant; ITD, internal tandem duplication; IV, intravenous; LDAC, low-dose cytarabine; m+, mutation-positive; NCCN, National Comprehensive Cancer Network; RBC, red blood cell; R/R, relapsed or refractory; SC, subcutaneous; TKD, tyrosine kinase domain  
  Select Safety Information  
  Posterior Reversible Encephalopathy Syndrome (PRES) 1% of 319 patients treated with XOSPATA in the clinical trials experienced posterior reversible encephalopathy syndrome (PRES) with symptoms including seizure and altered mental status. Symptoms have resolved after discontinuation of XOSPATA. A diagnosis of PRES requires confirmation by brain imaging, preferably magnetic resonance imaging (MRI). Discontinue XOSPATA in patients who develop PRES.  
 
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)
recommend gilteritinib (XOSPATA) as a treatment option for patients
with relapsed or refractory AML with a FLT3 mutation3
 
  Indication  
  XOSPATA is indicated for the treatment of adult patients who have relapsed or refractory acute myeloid leukemia (AML) with a FMS-like tyrosine kinase 3 (FLT3) mutation as detected by an FDA-approved test.  
  Important Safety Information  
  Contraindications  
  XOSPATA is contraindicated in patients with hypersensitivity to gilteritinib or any of the excipients. Anaphylactic reactions have been observed in clinical trials.  
 
WARNING: DIFFERENTIATION SYNDROME
Patients treated with XOSPATA have experienced symptoms of differentiation syndrome, which can be fatal or life-threatening if not treated. Symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, or renal dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.
 
  Warnings and Precautions  
  Differentiation Syndrome (See BOXED WARNING) 3% of 319 patients treated with XOSPATA in the clinical trials experienced differentiation syndrome. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal if not treated. Symptoms of differentiation syndrome in patients treated with XOSPATA included fever, dyspnea, pleural effusion, pericardial effusion, pulmonary edema, hypotension, rapid weight gain, peripheral edema, rash, and renal dysfunction. Some cases had concomitant acute febrile neutrophilic dermatosis. Differentiation syndrome occurred as early as 2 days and up to 75 days after XOSPATA initiation and has been observed with or without concomitant leukocytosis. If differentiation syndrome is suspected, initiate dexamethasone 10 mg IV every 12 hours (or an equivalent dose of an alternative oral or IV corticosteroid) and hemodynamic monitoring until improvement. Taper corticosteroids after resolution of symptoms and administer corticosteroids for a minimum of 3 days. Symptoms of differentiation syndrome may recur with premature discontinuation of corticosteroid treatment. If severe signs and/or symptoms persist for more than 48 hours after initiation of corticosteroids, interrupt XOSPATA until signs and symptoms are no longer severe.  
  Posterior Reversible Encephalopathy Syndrome (PRES) 1% of 319 patients treated with XOSPATA in the clinical trials experienced posterior reversible encephalopathy syndrome (PRES) with symptoms including seizure and altered mental status. Symptoms have resolved after discontinuation of XOSPATA. A diagnosis of PRES requires confirmation by brain imaging, preferably magnetic resonance imaging (MRI). Discontinue XOSPATA in patients who develop PRES.  
  Prolonged QT Interval XOSPATA has been associated with prolonged cardiac ventricular repolarization (QT interval). 1% of the 317 patients with a post-baseline QTc measurement on treatment with XOSPATA in the clinical trial were found to have a QTc interval greater than 500 msec and 7% of patients had an increase from baseline QTc greater than 60 msec. Perform electrocardiogram (ECG) prior to initiation of treatment with XOSPATA, on days 8 and 15 of cycle 1, and prior to the start of the next two subsequent cycles. Interrupt and reduce XOSPATA dosage in patients who have a QTcF >500 msec. Hypokalemia or hypomagnesemia may increase the QT prolongation risk. Correct hypokalemia or hypomagnesemia prior to and during XOSPATA administration.  
  Pancreatitis 4% of 319 patients treated with XOSPATA in the clinical trials experienced pancreatitis. Evaluate patients who develop signs and symptoms of pancreatitis. Interrupt and reduce the dose of XOSPATA in patients who develop pancreatitis.  
  Embryo-Fetal Toxicity XOSPATA can cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with XOSPATA and for at least 6 months after the last dose of XOSPATA. Advise males with female partners of reproductive potential to use effective contraception during treatment with XOSPATA and for at least 4 months after the last dose of XOSPATA. Pregnant women, patients becoming pregnant while receiving XOSPATA or male patients with pregnant female partners should be apprised of the potential risk to the fetus.  
  Adverse Reactions  
  Fatal adverse reactions occurred in 2% of patients receiving XOSPATA. These were cardiac arrest (1%) and one case each of differentiation syndrome and pancreatitis. The most frequent (≥5%) nonhematological serious adverse reactions reported in patients were fever (13%), dyspnea (9%), renal impairment (8%), transaminase increased (6%) and noninfectious diarrhea (5%).  
  7% discontinued XOSPATA treatment permanently due to an adverse reaction. The most common (>1%) adverse reactions leading to discontinuation were aspartate aminotransferase increased (2%) and alanine aminotransferase increased (2%).  
  The most frequent (≥5%) grade ≥3 nonhematological adverse reactions reported in patients were transaminase increased (21%), dyspnea (12%), hypotension (7%), mucositis (7%), myalgia/arthralgia (7%), and fatigue/malaise (6%).  
  Other clinically significant adverse reactions occurring in ≤10% of patients included: electrocardiogram QT prolonged (9%), hypersensitivity (8%), pancreatitis (5%), cardiac failure (4%), pericardial effusion (4%), acute febrile neutrophilic dermatosis (3%), differentiation syndrome (3%), pericarditis/myocarditis (2%), large intestine perforation (1%), and posterior reversible encephalopathy syndrome (1%).  
  Lab Abnormalities Shifts to grades 3-4 nonhematologic laboratory abnormalities in XOSPATA treated patients included phosphate decreased (14%), alanine aminotransferase increased (13%), sodium decreased (12%), aspartate aminotransferase increased (10%), calcium decreased (6%), creatine kinase increased (6%), triglycerides increased (6%), creatinine increased (3%), and alkaline phosphatase increased (2%).  
  Drug Interactions  
  Combined P-gp and Strong CYP3A Inducers Concomitant use of XOSPATA with a combined P-gp and strong CYP3A inducer decreases XOSPATA exposure which may decrease XOSPATA efficacy. Avoid concomitant use of XOSPATA with combined P-gp and strong CYP3A inducers.  
  Strong CYP3A inhibitors Concomitant use of XOSPATA with a strong CYP3A inhibitor increases XOSPATA exposure. Consider alternative therapies that are not strong CYP3A inhibitors. If the concomitant use of these inhibitors is considered essential for the care of the patient, monitor patient more frequently for XOSPATA adverse reactions. Interrupt and reduce XOSPATA dosage in patients with serious or life-threatening toxicity.  
  Drugs that Target 5HT2B Receptor or Sigma Nonspecific Receptor Concomitant use of XOSPATA may reduce the effects of drugs that target the 5HT2B receptor or the sigma nonspecific receptor (e.g., escitalopram, fluoxetine, sertraline). Avoid concomitant use of these drugs with XOSPATA unless their use is considered essential for the care of the patient.  
  Specific Populations  
  Lactation Advise women not to breastfeed during treatment with XOSPATA and for 2 months after the last dose.  
  Click here for Full Prescribing Information including BOXED WARNING for additional safety information.  
  Contact your GPO Account Manager to learn more.  
  References: 1. XOSPATA [package insert]. Northbrook, IL: Astellas Pharma US, Inc. 2. Astellas. XOSPATA. Data on File. 3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia v3.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed 05-07-2019. To view the most recent and complete version of the guideline, go online to NCCN.org. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.  
  © 2019 Astellas Pharma US, Inc. All rights reserved. 077-0575-PM 6/19
XOSPATA, Astellas, and the flying star logo are registered trademarks of Astellas Pharma Inc.
 
 
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