Lynparza (olaparib)

Lynparza is a prescription medicine used to treat adults who have:

• advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer with a certain type of inherited (germline) or acquired (somatic) abnormal BRCA gene. Lynparza is used alone as maintenance treatment after the cancer has responded to your first treatment with platinum-based chemotherapy. Your healthcare provider will perform a test to make sure that Lynparza is right for you.
• advanced ovarian cancer, fallopian tube cancer or primary peritoneal cancer with a certain type of abnormal BRCA gene or a positive laboratory tumor test for genomic instability called HRD. Lynparza is used in combination with another anti-cancer medicine, bevacizumab, as maintenance treatment after the cancer has responded to your first treatment with platinum-based chemotherapy. Your healthcare provider will perform a test to make sure that Lynparza is right for you.
• ovarian cancer, fallopian tube cancer, or primary peritoneal cancer, as maintenance treatment, when the cancer has come back. Lynparza is used after the cancer has responded to treatment with platinum-based chemotherapy.
• advanced ovarian cancer with a certain type of abnormal inherited BRCA gene, and have received treatment with 3 or more prior types of chemotherapy medicines. Your healthcare provider will perform a test to make sure that Lynparza is right for you.
• a certain type of abnormal inherited BRCA gene, human epidermal growth factor receptor 2 (HER2)-negative breast cancer that has spread to other parts of the body (metastatic). You should have received chemotherapy medicines, either before or after your cancer has spread. If you have hormone receptor (HR)-positive disease, you should have been treated with hormonal therapy. Your healthcare provider will perform a test to make sure that Lynparza is right for you.
• metastatic pancreatic cancer with a certain type of abnormal inherited BRCA gene. Lynparza is used as maintenance treatment after your cancer has not progressed on at least 16 weeks of treatment with platinum-based chemotherapy. Your healthcare provider will perform a test to make sure that Lynparza is right for you.

It is not known if Lynparza is safe and effective in children.

Lynparza may cause serious side effects.

The most common side effects of Lynparza are:

• nausea or vomiting. Tell your healthcare provider if you get nausea or vomiting. Your healthcare provider may prescribe medicines to treat these symptoms.
  • low number of red or white blood cells
  • stomach-area (abdominal) pain
  • dizziness
  • tiredness or weakness
  • sore throat or runny nose
  • diarrhea
  • joint, muscle, and back pain
  • headache
  • constipation
  • mouth sores
  • respiratory tract infections
  • changes in kidney function blood test
  • changes in the way food tastes
  • loss of appetite
  • low number of platelets
  • indigestion or heartburn

These are not all of the possible side effects of Lynparza.

Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Patient Selection

Information on FDA-approved tests for the detection of genetic mutations is available at http://www.fda.gov/companiondiagnostics.

Select patients for treatment with Lynparza based on the presence of deleterious or suspected deleterious HRR gene mutations, including BRCA mutations, or genomic instability based on the indication, biomarker, and sample type (Table 1).

Table 1 : Biomarker Testing for Patient Selection

Recommended Dosage

• The recommended dosage of Lynparza is 300 mg taken orally twice daily, with or without food.
• If a patient misses a dose of Lynparza, instruct patient to take their next dose at its scheduled time.
• Instruct patients to swallow tablets whole. Do not chew, crush, dissolve, or divide tablet.

First-Line Maintenance Treatment Of BRCA-mutated Advanced Ovarian Cancer

• Continue treatment until disease progression, unacceptable toxicity, or completion of 2 years of treatment.
• Patients with a complete response (no radiological evidence of disease) at 2 years should stop treatment. Patients with evidence of disease at 2 years, who in the opinion of the treating healthcare provider can derive further benefit from continuous treatment, can be treated beyond 2 years.

First-Line Maintenance Treatment Of HRD-positive Advanced Ovarian Cancer In Combination With Bevacizumab

• Continue Lynparza treatment until disease progression, unacceptable toxicity, or completion of 2 years of treatment.
• Patients with a complete response (no radiological evidence of disease) at 2 years should stop treatment.
• Patients with evidence of disease at 2 years, who in the opinion of the treating healthcare provider can derive further benefit from continuous Lynparza treatment, can be treated beyond 2 years.
• When used with Lynparza, the recommended dose of bevacizumab is 15 mg/kg every three weeks.
• Bevacizumab should be given for a total of 15 months including the period given with chemotherapy and given as maintenance. Refer to the Prescribing Information for bevacizumab when used in combination with Lynparza for more information.

Recurrent Ovarian Cancer, Germline BRCAm Advanced Ovarian Cancer, HER2-negative Metastatic Breast Cancer, Metastatic Pancreatic Adenocarcinoma, And HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer

Continue treatment until disease progression or unacceptable toxicity for:

• Maintenance treatment of recurrent ovarian cancer
• Advanced germline BRCA-mutated ovarian cancer
• Germline BRCA-mutated HER-2 negative metastatic breast cancer
• First-line maintenance treatment of germline BRCA-mutated metastatic pancreatic adenocarcinoma.
• HRR gene-mutated metastatic castration-resistant prostate cancer
• Patients receiving Lynparza for mCRPC should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy.

Dosage Modifications For Adverse Reactions

• To manage adverse reactions, consider interruption of treatment or dose reduction. The recommended dose reduction is 250 mg taken twice daily.
• If a further dose reduction is required, then reduce to 200 mg taken twice daily.

Dosage Modifications For Concomitant Use With Strong Or Moderate CYP3A Inhibitors

Avoid concomitant use of strong or moderate CYP3A inhibitors with Lynparza. If concomitant use cannot be avoided, reduce Lynparza dosage to:

• 100 mg twice daily when used concomitantly with a strong CYP3A inhibitor.
• 150 mg twice daily when used concomitantly with a moderate CYP3A inhibitor.

After the inhibitor has been discontinued for 3 to 5 elimination half-lives, resume the Lynparza dose taken prior to initiating the CYP3A inhibitor.

Dosage Modifications For Renal Impairment

Moderate Renal Impairment

• In patients with moderate renal impairment (CLcr 31-50 mL/min), reduce the Lynparza dosage to 200 mg orally twice daily.

Use With Anticancer Agents

Clinical studies of Lynparza with other myelosuppressive anticancer agents, including DNA damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity.

Effect Of Other Drugs On Lynparza

Strong And Moderate CYP3A Inhibitors

• Coadministration of CYP3A inhibitors can increase olaparib concentrations, which may increase the risk for adverse reactions.
• Avoid coadministration of strong or moderate CYP3A inhibitors.
• If the strong or moderate inhibitor must be coadministered, reduce the dose of Lynparza.

Strong And Moderate CYP3A Inducers

• Concomitant use with a strong or moderate CYP3A inducer decreased olaparib exposure, which may reduce Lynparza efficacy.
• Avoid coadministration of strong or moderate CYP3A inducers.

• Based on findings in animals and its mechanism of action, Lynparza can cause fetal harm when administered to a pregnant woman.
• There are no available data on Lynparza use in pregnant women to inform the drug-associated risk.
• In an animal reproduction study, the administration of olaparib to pregnant rats during the period of organogenesis caused teratogenicity and embryo-fetal toxicity at exposures below those in patients receiving the recommended human dose of 300 mg twice daily.
• No data are available regarding the presence of olaparib in human milk, or on its effects on the breastfed infant or on milk production.
• Because of the potential for serious adverse reactions in the breastfed infants from Lynparza, advise a lactating woman not to breastfeed during treatment with Lynparza and for one month after receiving the last dose.