|
Treatment with XALKORI should be initiated and supervised by a physician experienced in the use of anticancer medicinal products.
ALK testing
An accurate and validated ALK assay is necessary for the selection of patients for treatment with XALKORI (see section 5.1 for information on assays used in the trials).
Assessment for ALK-positive NSCLC should be performed by laboratories with demonstrated proficiency in the specific technology being utilised.
Posology
The recommended dose schedule of XALKORI is 250 mg twice daily (500 mg daily) taken continuously. Treatment should be continued until disease progression or unacceptable toxicity. Prolongation of treatment after objective disease progression in selected patients may be considered on an individual basis, but no additional benefit has been demonstrated.
If a dose is missed, then it should be taken as soon as the patient remembers unless it is less than 6 hours until the next dose, in which case the patient should not take the missed dose. Patients should not take 2 doses at the same time to make up for a missed dose.
Dose adjustments
Dosing interruption and/or dose reduction may be required based on individual safety and tolerability. If dose reduction is necessary, then the dose of XALKORI should be reduced to 200 mg taken twice daily. If further dose reduction is necessary, then the dose should be modified to 250 mg taken once daily based on individual safety and tolerability. Dose reduction guidelines for hematologic and non-hematologic toxicities are provided in Tables 1 and 2.
Table 1. XALKORI dose modification – Hematologic toxicitiesa
|
CTCAEb Grade
|
XALKORI treatment
|
|
Grade 3
|
Withhold until recovery to Grade ≤2, then resume at the same dose schedule
|
|
Grade 4
|
Withhold until recovery to Grade ≤2, then resume at 200 mg twice dailyc
|
aExcept lymphopenia
bNational Cancer Institute (NCI) Common Terminology Criteria for Adverse Events
cIn case of recurrence, dosing should be withheld until recovery to Grade ≤2, then dosing should be resumed at 250 mg once daily. XALKORI must be permanently discontinued in case of further Grade 4 recurrence.
Table 2. XALKORI dose modification – Non-hematologic toxicities
|
CTCAEa Grade
|
XALKORI treatment
|
|
Grade 3 or 4 alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation with Grade ≤1 total bilirubin
|
Withhold until recovery to Grade ≤1 or baseline, then resume at 200 mg twice dailyb
|
|
Grade 2, 3 or 4 ALT or AST elevation with concurrent Grade 2, 3 or 4 total bilirubin elevation (in the absence of cholestasis or hemolysis)
|
Permanently discontinue
|
|
Any Grade pneumonitisc
|
Permanently discontinue
|
|
Grade 3 QTc prolongation
|
Withhold until recovery to Grade ≤1, then resume at 200 mg twice dailyb
|
|
Grade 4 QTc prolongation
|
Permanently discontinue
|
aNCI Common Terminology Criteria for Adverse Events
bIn case of recurrence, dosing should be withheld until recovery to Grade ≤1, then dosing should be resumed at 250 mg once daily. XALKORI must be permanently discontinue in case of further Grade 3 or 4 recurrence.
cNot attributable to NSCLC progression, other pulmonary disease, infection, or radiation effect. XALKORI should be withheld if pneumonitis is suspected, and must be permanently discontinued if treatment-related pneumonitis is diagnosed.
Hepatic impairment
XALKORI has not been studied in patients with hepatic impairment. Clinical studies that were conducted excluded patients with AST or ALT >2.5 x upper limit of normal (ULN), or if due to underlying malignancy, >5.0 x ULN or with total bilirubin >1.5 x ULN. Treatment with XALKORI should be used with caution in patients with mild and moderate hepatic impairment (see Table 2 and section 4.8). XALKORI should not be used in patients with severe hepatic impairment (see section 4.3).
Renal impairment
No starting dose adjustment is recommended for patients with mild (60 ≤ creatinine clearance [CLcr] < 90 mL/min) or moderate (30 ≤ CLcr < 60 mL/min) renal impairment, since the population pharmacokinetic analysis indicated no clinically meaningful changes in steady-state crizotinib exposure in these patients. Crizotinib plasma concentrations may be increased in patients with severe renal impairment (CLcr <30 mL/min). The crizotinib dose should be adjusted to 250 mg taken orally once daily in patients with severe renal impairment not requiring peritoneal dialysis or hemodialysis. The dose may be increased to 200 mg twice daily based on individual safety and tolerability after at least 4 weeks of treatment (see sections 4.4 and 5.2).
Elderly
Clinical studies of XALKORI did not include sufficient numbers of patients aged 65 years or older to determine whether they respond differently from younger patients. Of the 125 patients in Study A, 18 (14%) were 65 years or older. Of the 261 patients in Study B, 30 (11%) were 65 years or older (see section 5.2). Considering the limited data available in this subgroup of patients, no formal dosing recommendation can be made until additional data become available.
Paediatric population
The safety and efficacy of XALKORI in paediatric patients has not been established. No data are available.
Method of administra |
