SAFETY AND TOLERABILITY

Safety and tolerability of LYNPARZA in patients with gBRCAm, HER2-negative metastatic breast cancer1

Grades 1-4 adverse reactions1,*

Grades 3-4 adverse reactions1,*

Grades 1-4 adverse reactions in ≥20% of patients with gBRCAm, HER2-negative mBC who received LYNPARZA1,*

Grades 1-4 adverse reactions in ≥20% of patients with gBRCAm, HER2-negative mBC who received LYNPARZA® (olaparib) or chemotherapy.

In addition, adverse reactions in OlympiAD that occurred in <20% of patients receiving LYNPARZA were cough, decreased appetite, thrombocytopenia, dysgeusia, lymphopenia, dizziness, dyspepsia, stomatitis, upper abdominal pain, rash, increase in serum creatinine, and dermatitis.1

  gBRCAm=germline BRCA-mutated; HER2=human epidermal growth factor receptor 2; mBC=metastatic breast cancer.

*Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0.

Represents grouped terms consisting of anemia (PTs=anemia, erythropenia, hematocrit decreased, hemoglobin decreased, and red blood cell count decreased).

Represents grouped terms consisting of bronchitis, influenza, lower respiratory tract infection, nasopharyngitis, pharyngitis, respiratory tract infection, rhinitis, sinusitis, upper respiratory tract infection, and upper respiratory tract infection bacterial.

§Represents grouped terms of related terms that reflect the medical concept of neutropenia (PTs=febrile neutropenia, granulocyte count decreased, granulocytopenia, neutropenia, neutropenic infection, neutropenic sepsis, neutrophil count decreased).

||Represents grouped terms consisting of leukopenia and white blood cell count decreased.

Chemotherapy of health care provider’s choice included capecitabine, eribulin, or vinorelbine.1,2

Grades 3-4 adverse reactions in patients on LYNPARZA or on chemotherapy1,2,*,†,‡

Grades 3-4 adverse reactions in patients on LYNPARZA® (olaparib) or on chemotherapy.

36.6%LYNPARZA Tablets

50.5%Health Care Provider’s Choice Chemotherapy

  gBRCAm=germline BRCA-mutated; HER2=human epidermal growth factor receptor 2; mBC=metastatic breast cancer.

*Graded according to NCI CTCAE, version 4.0.

Chemotherapy of health care provider’s choice included capecitabine, eribulin, or vinorelbine.1,2

Includes Grade 3-4 in those adverse reactions seen in ≥20% of patients with gBRCAm, HER2-negative mBC.

§Represents grouped terms consisting of anemia (PTs=anemia, erythropenia, hematocrit decreased, hemoglobin decreased, and red blood cell count decreased).

||Represents grouped terms of related terms that reflect the medical concept of neutropenia (PTs=febrile neutropenia, granulocyte count decreased, granulocytopenia, neutropenia, neutropenic infection, neutropenic sepsis, neutrophil count decreased).

Represents grouped terms consisting of leukopenia and white blood cell count decreased.

#Represents grouped terms consisting of bronchitis, influenza, lower respiratory tract infection, nasopharyngitis, pharyngitis, respiratory tract infection, rhinitis, sinusitis, upper respiratory tract infection, and upper respiratory tract infection bacterial.

Grades 1-4 laboratory abnormalities1

Grades 3-4 laboratory abnormalities1

Grades 1-4 laboratory abnormalities reported in ≥25% of patients in OlympiAD1

  LYNPARZA Tablets (n=205)* Health Care Provider’s Choice Chemotherapy (n=91)*,†
Laboratory Parameter Grades 1-4 (%) Grades 1-4 (%)
Increase in mean corpuscular volume§ 71 33
Decrease in hemoglobin 82 66
Decrease in leukocytes 71 70
Decrease in lymphocytes 73 63
Decrease in absolute neutrophil count 46 65
Decrease in platelets 33 28

*This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.

Chemotherapy of health care provider’s choice included capecitabine, eribulin, or vinorelbine.1,2

Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.

§Represents the proportion of subjects whose mean corpuscular volume was > ULN.

Grades 3-4 laboratory abnormalities reported in patients on LYNPARZA or on chemotherapy1,*

  LYNPARZA Tablets (n=205) Health Care Provider’s Choice Chemotherapy (n=91)†,‡
Laboratory Parameter§ Grades 3-4 (%) Grades 3-4 (%)
Increase in mean corpuscular volume|| - -
Decrease in hemoglobin 17 3
Decrease in leukocytes 8 23
Decrease in lymphocytes 21 3
Decrease in absolute neutrophil count 11 38
Decrease in platelets 3 0

*Includes Grade 3-4 in those laboratory abnormalities seen in ≥25% of patients with gBRCAm, HER2-negative mBC.

This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.

Chemotherapy of health care provider’s choice included capecitabine, eribulin, or vinorelbine.1,2

§Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.

||Represents the proportion of subjects whose mean corpuscular volume was > ULN.

Safety and tolerability of LYNPARZA in patients with gBRCAm, HER2-negative metastatic breast cancer1

95% continued treatment with LYNPARZA without adverse reaction-related discontinuation and 92% on chemotherapy

  LYNPARZA Tablets Health Care Provider’s Choice Chemotherapy*
  • Median duration of treatment was 8.2 months with LYNPARZA and 3.4 months with chemotherapy1,*
*Chemotherapy of health care provider’s choice included capecitabine, eribulin, or vinorelbine.1,2 gBRCAm=germline BRCA-mutated; HER2=human epidermal growth factor receptor 2; mBC=metastatic breast cancer.

 

INDICATIONS

LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:

  • For the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy

  • For the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with 3 or more prior lines of chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

There are no contraindications for LYNPARZA.

WARNINGS AND PRECAUTIONS

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in <1.5% of patients exposed to LYNPARZA monotherapy, and the majority of events had a fatal outcome. The duration of therapy in patients who developed secondary MDS/AML varied from <6 months to >2 years. All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy, and some also had a history of more than one primary malignancy or of bone marrow dysplasia.

Do not start LYNPARZA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete blood count for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities, interrupt LYNPARZA and monitor blood count weekly until recovery.

If the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed.

Pneumonitis: Occurred in <1% of patients exposed to LYNPARZA, and some cases were fatal. If patients present with new or worsening respiratory symptoms such as dyspnea, cough, and fever, or a radiological abnormality occurs, interrupt LYNPARZA treatment and initiate prompt investigation. Discontinue LYNPARZA if pneumonitis is confirmed and treat patient appropriately.

Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. A pregnancy test is recommended for females of reproductive potential prior to initiating treatment.

Females

Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months following the last dose.

ADVERSE REACTIONS—Maintenance Setting

Most common adverse reactions (Grades 1-4) in ≥20% of patients in clinical trials of LYNPARZA in the maintenance setting for SOLO-2: nausea (76%), fatigue (including asthenia) (66%), anemia (44%), vomiting (37%), nasopharyngitis/upper respiratory tract infection (URI)/influenza (36%), diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%), headache (26%), decreased appetite (22%), and stomatitis (20%).

Study 19: nausea (71%), fatigue (including asthenia) (63%), vomiting (35%), diarrhea (28%), anemia (23%), respiratory tract infection (22%), constipation (22%), headache (21%), and decreased appetite (21%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA in the maintenance setting (SOLO-2/Study 19) were: increase in mean corpuscular volume (89%/82%), decrease in hemoglobin (83%/82%), decrease in leukocytes (69%/58%), decrease in lymphocytes (67%/52%), decrease in absolute neutrophil count (51%/47%), increase in serum creatinine (44%/45%), and decrease in platelets (42%/36%).

ADVERSE REACTIONS—Advanced gBRCAm ovarian cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients in clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer after 3 or more lines of chemotherapy (pooled from 6 studies) were: fatigue (including asthenia) (66%), nausea (64%), vomiting (43%), anemia (34%), diarrhea (31%), nasopharyngitis/upper respiratory tract infection (URI) (26%), dyspepsia (25%), myalgia (22%), decreased appetite (22%), and arthralgia/musculoskeletal pain (21%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer (pooled from 6 studies) were: decrease in hemoglobin (90%), increase in mean corpuscular volume (57%), decrease in lymphocytes (56%), increase in serum creatinine (30%), decrease in platelets (30%), and decrease in absolute neutrophil count (25%).

DRUG INTERACTIONS

Anticancer Agents: Clinical studies of LYNPARZA in combination with other myelosuppressive anticancer agents, including DNA-damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity.

CYP3A Inhibitors: Avoid concomitant use of strong or moderate CYP3A inhibitors. If a strong or moderate CYP3A inhibitor must be co-administered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during LYNPARZA treatment.

CYP3A Inducers: Avoid concomitant use of strong or moderate CYP3A inducers when using LYNPARZA. If a moderate inducer cannot be avoided, there is a potential for decreased efficacy of LYNPARZA.

USE IN SPECIFIC POPULATIONS

Lactation: No data are available regarding the presence of olaparib in human milk, its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in the breastfed infant, advise a lactating woman not to breastfeed during treatment with LYNPARZA and for 1 month after receiving the final dose.

Pediatric Use: The safety and efficacy of LYNPARZA have not been established in pediatric patients.

Hepatic Impairment: No adjustment to the starting dose is required in patients with mild hepatic impairment (Child-Pugh classification A). There are no data in patients with moderate or severe hepatic impairment.

Renal Impairment: No adjustment to the starting dose is necessary in patients with mild renal impairment (CLcr=51-80 mL/min). In patients with moderate renal impairment (CLcr=31-50 mL/min), reduce the dose to 200 mg twice daily. There are no data in patients with severe renal impairment or end-stage renal disease (CLcr ≤30 mL/min).

DOSING AND ADMINISTRATION

To avoid substitution errors and overdose, do not substitute LYNPARZA tablets with LYNPARZA capsules on a milligram-to-milligram basis due to differences in the dosing and bioavailability of each formulation. Recommended tablet dose is 300 mg, taken orally twice daily, with or without food. Continue treatment until disease progression or unacceptable toxicity. For adverse reactions, consider dose interruption or dose reduction.

Please see complete Prescribing Information, including Patient Information (Medication Guide).

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-10881-800-FDA-1088.

 

INDICATION

LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated in patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

There are no contraindications for LYNPARZA.

WARNINGS AND PRECAUTIONS

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in <1.5% of patients exposed to LYNPARZA monotherapy, and the majority of events had a fatal outcome. The duration of therapy in patients who developed secondary MDS/AML varied from <6 months to >2 years. All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy, and some also had a history of more than one primary malignancy or of bone marrow dysplasia.

Do not start LYNPARZA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete blood count for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities, interrupt LYNPARZA and monitor blood count weekly until recovery.

If the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed.

Pneumonitis: Occurred in <1% of patients exposed to LYNPARZA, and some cases were fatal. If patients present with new or worsening respiratory symptoms such as dyspnea, cough, and fever, or a radiological abnormality occurs, interrupt LYNPARZA treatment and initiate prompt investigation. Discontinue LYNPARZA if pneumonitis is confirmed and treat patient appropriately.

Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. A pregnancy test is recommended for females of reproductive potential prior to initiating treatment.

Females
Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months following the last dose.

Males
Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 3 months following the last dose of LYNPARZA and to not donate sperm during this time.

ADVERSE REACTIONS

Most common adverse reactions (Grades 1-4) in ≥20% of patients in OlympiAD were: nausea (58%), anemia (40%), fatigue (including asthenia) (37%), vomiting (30%), neutropenia (27%), respiratory tract infection (27%), leukopenia (25%), diarrhea (21%), and headache (20%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in OlympiAD were: decrease in hemoglobin (82%), decrease in lymphocytes (73%), decrease in leukocytes (71%), increase in mean corpuscular volume (71%), decrease in absolute neutrophil count (46%), and decrease in platelets (33%).

DRUG INTERACTIONS

Anticancer Agents: Clinical studies of LYNPARZA in combination with other myelosuppressive anticancer agents, including DNA-damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity.

CYP3A Inhibitors: Avoid concomitant use of strong or moderate CYP3A inhibitors. If a strong or moderate CYP3A inhibitor must be co-administered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during LYNPARZA treatment.

CYP3A Inducers: Avoid concomitant use of strong or moderate CYP3A inducers when using LYNPARZA. If a moderate inducer cannot be avoided, there is a potential for decreased efficacy of LYNPARZA.

USE IN SPECIFIC POPULATIONS

Lactation: No data are available regarding the presence of olaparib in human milk, its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in the breastfed infant, advise a lactating woman not to breastfeed during treatment with LYNPARZA and for 1 month after receiving the final dose.

Pediatric Use: The safety and efficacy of LYNPARZA have not been established in pediatric patients.

Hepatic Impairment: No adjustment to the starting dose is required in patients with mild hepatic impairment (Child-Pugh classification A). There are no data in patients with moderate or severe hepatic impairment.

Renal Impairment: No adjustment to the starting dose is necessary in patients with mild renal impairment (CLcr=51-80 mL/min). In patients with moderate renal impairment (CLcr=31-50 mL/min), reduce the dose to 200 mg twice daily. There are no data in patients with severe renal impairment or end-stage renal disease (CLcr ≤30 mL/min).

Please see complete Prescribing Information, including Patient Information (Medication Guide).

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