Usual Adult Dose for Ovarian Cancer

300 mg orally once a day until disease progression or unacceptable toxicity

Comments:

• Initiate therapy with this drug no later than 8 weeks after a patient's most recent platinum-containing regimen.
• Information on FDA-approved tests for the detection of either deleterious or suspected deleterious BRCA mutation or genomic instability for this indication is available at: http://www.fda.gov/CompanionDiagnostics.

Uses:

• For maintenance therapy of recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy
• For treatment of adult patients with advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with 3 or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either:

a deleterious or suspected deleterious BRCA mutation
OR
genomic instability and who have progressed more than 6 months after response to the last platinum-based chemotherapy

Usual Adult Dose for Fallopian Tube Cancer

300 mg orally once a day until disease progression or unacceptable toxicity

Comments:

• Initiate therapy with this drug no later than 8 weeks after a patient's most recent platinum-containing regimen.
• Information on FDA-approved tests for the detection of either deleterious or suspected deleterious BRCA mutation or genomic instability for this indication is available at: http://www.fda.gov/CompanionDiagnostics.

Uses:

• For maintenance therapy of recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy
• For treatment of adult patients with advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with 3 or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either:

a deleterious or suspected deleterious BRCA mutation
OR
genomic instability and who have progressed more than 6 months after response to the last platinum-based chemotherapy

Usual Adult Dose for Peritoneal Cancer

300 mg orally once a day until disease progression or unacceptable toxicity

Comments:

• Initiate therapy with this drug no later than 8 weeks after a patient's most recent platinum-containing regimen.
• Information on FDA-approved tests for the detection of either deleterious or suspected deleterious BRCA mutation or genomic instability for this indication is available at: http://www.fda.gov/CompanionDiagnostics.

Uses:

• For maintenance therapy of recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy
• For treatment of adult patients with advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with 3 or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either:

a deleterious or suspected deleterious BRCA mutation
OR
genomic instability and who have progressed more than 6 months after response to the last platinum-based chemotherapy

Renal Dose Adjustments

Mild to moderate renal impairment (CrCl 30 to 89 mL/min): No adjustment recommended.
Severe renal impairment or end stage renal impairment: Data not available

Liver Dose Adjustments

Mild hepatic impairment: No adjustment recommended.
Moderate to severe hepatic impairment: Data not available

Dose Adjustments

Consider therapy interruption, dose reduction, and/or therapy discontinuation to manage adverse reactions (ARs):

• Starting dose: 300 mg orally once a day
• First dose reduction: 200 mg orally once a day
• Second dose reduction: 100 mg orally once a day
• Further dose reduction below 100 mg/day required: Discontinue therapy.

NONHEMATOLOGIC ADVERSE REACTIONS (AR):
GRADE 3 OR GREATER AR WHERE PROPHYLAXIS IS NOT CONSIDERED FEASIBLE OR AR PERSISTS DESPITE TREATMENT:

• Withhold therapy for a maximum of 28 days or until resolution of AR.
• Resume therapy at reduced dose; up to 2 dose reductions are permitted.

GRADE 3 OR GREATER THERAPY-RELATED AR LASTING MORE THAN 28 DAYS WHILE PATIENT IS ADMINISTERED DOSE OF 100 MG/DAY: Discontinue therapy.

HEMATOLOGIC ARs: Monitor complete blood counts weekly for the first month, monthly for the next 11 months, and periodically after:
PLATELET COUNT LESS THAN 100,000/mcL:
FIRST OCCURRENCE:

• Withhold therapy for a maximum of 28 days and monitor blood counts weekly until platelet counts return to 100,000/mcL or more.
• Resume therapy at same or reduced dose.
• If platelets less than 75,000/mcL, resume at a reduced dose.

SECOND OCCURRENCE:

• Withhold therapy for a maximum of 28 days and monitor blood counts weekly until platelet counts return to 100,000/mcL or more.
• Resume therapy at reduced dose.
• Discontinue therapy if the platelet count has not returned to acceptable levels within 28 days of the dose interruption period, or if the patient has already undergone dose reduction to 100 mg once a day.

NEUTROPHILS LESS THAN 1000/mcL OR HEMOGLOBIN LESS THAN 8 g/dL:

• Withhold therapy for a maximum of 28 days and monitor blood counts weekly until neutrophil counts return to 1500/mcL or more OR hemoglobin returns to 9 g/dL or more.
• Resume therapy at reduced dose.
• Discontinue therapy if neutrophils and/or hemoglobin have not returned to acceptable levels within 28 days of the dose interruption period, or if the patient has already undergone dose reduction to 100 mg once a day.

HEMATOLOGIC ADVERSE REACTION REQUIRING TRANSFUSION:

• Consider platelet transfusion for patients with platelet counts 10,000/mcL or less.
• If there are other risk factors such as coadministration of anticoagulation or antiplatelet drugs, consider interrupting these drugs and/or transfusion at a higher platelet count.
• Resume therapy at reduced dose.

MYELODYSPLASTIC SYNDROME OR ACUTE MYELOID LEUKEMIA (MDS/AML) IS CONFIRMED: Discontinue therapy.

Precautions

CONTRAINDICATIONS:

• Hypersensitivity to the active component or any of the ingredients
• None

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• This drug may be taken with or without food.
• Swallow capsules whole.
• Take this drug at approximately the same time each day.
• Bedtime administration may be a potential method for managing nausea.
• In the case of a missed or vomited dose, skip that dose and take the next dose at the regularly scheduled time.

Storage Requirements:

• Store at 20C to 25C (68F to 77F); excursions permitted between 15C to 30C (59F to 86 F).

General:

• Select patients for treatment of advanced ovarian cancer after 3 or more chemotherapy regimens associated with HRD positive status based on either deleterious or suspected deleterious BRCA mutation and/or genomic instability score (GIS).

Monitoring:

• Cardiovascular: Blood pressure and heart rate (monthly for the first year and periodically thereafter during therapy)
• Hematologic: CBC (weekly for the first month, monthly for the next 11 months of therapy, and periodically thereafter)