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Prescribing Information and
Important Safety Information
LYNPARZA® (olaparib) Logo
INDICATIONS
LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:
First-Line Maintenance BRCAm Advanced Ovarian Cancer
For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.
First-Line Maintenance HRD-Positive Advanced Ovarian Cancer in Combination with Bevacizumab
In combination with bevacizumab for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either:
a deleterious or suspected deleterious BRCA mutation, and/or
genomic instability
Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.
SELECT SAFETY INFORMATION
LYNPARZA is associated with serious, potentially fatal risks, including myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) and pneumonitis. LYNPARZA can also cause fetal harm.
Please see additional Important Safety Information below.
 
 
PAOLA-1 trial design
Patients must have received at least 3 cycles of bevacizumab in combination with platinum-based chemotherapy (~2 months). Only in the case of interval debulking surgery were 2 cycles of bevacizumab in combination with the last 3 cycles of platinum-based chemotherapy permitted.6
* BRCA mutation status was determined by local laboratories.
LYNPARZA or placebo was administered for up to 24 months or until disease progression or unacceptable toxicity. This study did not implement a prespecified crossover study design.
PAOLA-1 primary endpoint1:
Investigator-assessed PFS
Select secondary endpoints5,7‡:
Safety
Time from randomization until second disease progression or death
Time until first subsequent therapy or death
Overall survival
Prespecified exploratory analyses1,5‡:
PFS in predefined subgroups, including HRD status and BRCA mutation status
PFS within HRD-positive patients served as the basis of the
FDA-approved indication.
More endpoints than those noted here were studied in PAOLA-1. Not all results from these endpoints are detailed in this piece.7
Median PFS of 37.2 months with LYNPARZA + bevacizumab; KM curve
ESTIMATED PROPORTION OF PATIENTS FREE FROM PROGRESSION OR DEATH AT 2 YEARS1,5
The 2-year analysis is descriptive only; the PAOLA-1 trial was not powered to assess a statistical difference between treatment groups at these time points.
* Select patients for this indication based on an FDA-approved companion diagnostic.1
Including BRCA mutation (as determined by Myriad myChoice® CDx) and other causes of HRD. HRD positive is defined as either a tBRCA mutation and/or an HRD score ≥42 by Myriad myChoice® CDx.7
All trial participants were retrospectively evaluated for HRD using the Myriad myChoice® CDx.1∗
HRD-positive patients were defined as BRCAm or non-BRCAm with other biomarkers of HRD. In the PAOLA-1 trial, 48% of patients were HRD positive.5,7
48% of patients were HRD positive, which includes BRCAm and non-BRCAm patients
* HRD positive is defined as either a tBRCA mutation and/or an HRD score ≥42 by Myriad myChoice® CDx; HRD negative is defined as either non–tBRCA-mutated and/or an HRD score <42 by Myriad myChoice® CDx.7 4.2% of the test results were missing, 2.1% failed, and 11.3% were inconclusive, yielding approximately 18% of the total PAOLA-1 population with an unknown HRD status.8
In a prespecified exploratory analysis of HRD-negative and HRD-unknown patients, there was insufficient evidence to suggest differential efficacy between the combination of LYNPARZA + bevacizumab and bevacizumab + placebo.
Adverse reactions reported in ≥10% of patients
* Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0.
Includes asthenia and fatigue.
Includes anemia, anemia macrocytic, erythropenia, hematocrit decreased, hemoglobin decreased, normochromic anemia, normochromic normocytic anemia, normocytic anemia, and red blood cell count decreased.
§ Includes B-lymphocyte count decreased, lymphocyte count decreased, lymphopenia, and T-lymphocyte count decreased.
|| Includes leukopenia and white blood cell count decreased.
Fatal adverse reactions occurred in 1 patient due to concurrent pneumonia and aplastic anemia. Serious adverse reactions occurred in 31% of patients who received LYNPARZA + bevacizumab. Serious adverse reactions in >5% of patients included hypertension (19%) and anemia (17%).1
In addition, venous thromboembolic events occurred more commonly in patients receiving LYNPARZA + bevacizumab (5%) than in those receiving bevacizumab + placebo (1.9%)1
Common ARs with LYNPARZA were generally consistent with the known safety profile of LYNPARZA monotherapy1
Laboratory abnormalities reported in ≥25% of patients
Reported within 30 days of the last dose.
# 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.
∗∗ Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.
Approximately 1 in 2 women with advanced ovarian cancer is HRD positive
BRCA results are part of the HRD assay.12 Test cannot distinguish between germline and somatic mutations.12 If found to have a BRCA mutation, consult with a genetic counselor for germline testing to identify familial risk.
Test for HRD at diagnosis
Tumor tests cannot distinguish between germline and somatic mutations12
If found to have a BRCA mutation, consult with genetic counselor for germline testing to identify familial risk
HOW to test
At first tissue collection, order the Myriad myChoice® CDx* to determine patient’s HRD status1,12
Visit MyriadmyChoice.com for more information about ordering the Myriad myChoice® CDx
Partner with your pathologist for specimen handling and shipment
* HRD positive is defined as either a tBRCA mutation and/or an HRD score ≥42 by Myriad myChoice® CDx; HRD negative is defined as either non–tBRCA-mutated and/or an HRD score <42 by Myriad myChoice® CDx. HRD unknown is defined in accordance with a test that fails, is inconclusive, or is missing.7,8 Test determines HRD status by detecting BRCA1 and BRCA2 variants and assessing genomic instability.12
LYNPARZA monotherapy is a first-line maintenance therapy option for women with a BRCA mutation detected by an FDA-approved test who did not receive bevacizumab at induction.1
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommendations for olaparib (LYNPARZA) + bevacizumab
Olaparib (LYNPARZA) + bevacizumab is recommended in the NCCN Guidelines® as an option for maintenance therapy in patients with advanced ovarian cancer who are in complete or partial remission after surgery and platinum-based first-line chemotherapy + bevacizumab.17
CATEGORY 1* recommendation for patients with sBRCA1/2 or gBRCA1/2 mutations17
CATEGORY 2A recommendation for patients with BRCA1/2wt or unknown mutation status, including those with HRD-positive disease.17‡ Olaparib + bevacizumab is only FDA-approved for patients with HRD-positive advanced ovarian cancer, which includes some patients with BRCA1/2wt or unknown mutation status.1
  NCCN 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.
* Category 1: Based upon high-level evidence, there is uniform NCCN consensus (at least 85% of panel members) that the intervention is appropriate.17
Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus (at least 85% of panel members) that the intervention is appropriate.17
In the absence of a BRCA1/2 mutation, HRD status may provide information on the magnitude of benefit of PARP inhibitor therapy (category 2B§).17
§ Category 2B: Based upon lower-level evidence, there is NCCN consensus (≥50% and <85% of panel members) that the intervention is appropriate.17
LYNPARZA is indicated in combination with bevacizumab for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either1:
a deleterious or suspected deleterious BRCA mutation, and/or
genomic instability
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—First-Line Maintenance BRCAm Advanced Ovarian Cancer
Most common adverse reactions (Grades 1-4) in ≥10% of patients in clinical trials of LYNPARZA in the first-line maintenance setting for SOLO-1 were: nausea (77%), fatigue (67%), abdominal pain (45%), vomiting (40%), anemia (38%), diarrhea (37%), constipation (28%), upper respiratory tract infection/influenza/nasopharyngitis/bronchitis (28%), dysgeusia (26%), decreased appetite (20%), dizziness (20%), neutropenia (17%),
dyspepsia (17%), dyspnea (15%), leukopenia (13%), UTI (13%), thrombocytopenia (11%), and stomatitis (11%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA in the first-line maintenance setting for SOLO-1 were: decrease in hemoglobin (87%), increase in mean corpuscular volume (87%), decrease in leukocytes (70%), decrease in lymphocytes (67%), decrease in absolute neutrophil count (51%), decrease in platelets (35%), and increase in serum creatinine (34%).
ADVERSE REACTIONS—First-Line Maintenance Advanced Ovarian Cancer in Combination with Bevacizumab
Most common adverse reactions (Grades 1-4) in ≥10% of patients treated with LYNPARZA/bevacizumab compared to a ≥5% frequency for placebo/bevacizumab in the first-line maintenance setting for PAOLA-1 were: nausea (53%), fatigue (including asthenia) (53%), anemia (41%), lymphopenia (24%), vomiting (22%) and leukopenia (18%). In addition, the most common adverse reactions (≥10%) for patients receiving LYNPARZA/bevacizumab irrespective of the frequency compared with the placebo/bevacizumab arm were: diarrhea (18%), neutropenia (18%), urinary tract infection (15%) and headache (14%).
In addition, venous thromboembolic events occurred more commonly in patients receiving LYNPARZA/bevacizumab (5%) than in those receiving placebo/bevacizumab (1.9%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients for LYNPARZA in combination with bevacizumab in the first-line maintenance setting for PAOLA-1 were: decrease in hemoglobin (79%), decrease in lymphocytes (63%), increase in serum creatinine (61%), decrease in leukocytes (59%), decrease in absolute neutrophil count (35%) and decrease in platelets (35%).
DRUG INTERACTIONS
Anticancer Agents: Clinical studies of LYNPARZA with other myelosuppressive anticancer agents, including DNA-damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity.
CYP3A Inhibitors: Avoid coadministration of strong or moderate CYP3A inhibitors when using LYNPARZA. If a strong or moderate CYP3A inhibitor must be coadministered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during LYNPARZA treatment.
CYP3A Inducers: Avoid coadministration of strong or moderate CYP3A inducers when using 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 or moderate hepatic impairment (Child-Pugh classification A and B). There are no data in patients with severe hepatic impairment (Child-Pugh classification C).
Renal Impairment: No dosage modification is recommended in patients with mild renal impairment (CLcr 51-80 mL/min estimated by Cockcroft-Gault). In patients with moderate renal impairment (CLcr 31-50 mL/min), reduce the dose of LYNPARZA 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).
You may report side effects related to AstraZeneca products by clicking here.
AR=adverse reaction; BID=twice daily; BRCAm=BRCA-mutated; BRCAwt=BRCA wild-type; CI=confidence interval; gBRCA1/2=germline BRCA1/2; HR=hazard ratio; HRD=homologous recombination deficiency; HRR=homologous recombination repair; HRRm=homologous recombination repair mutation; ITT=intention-to-treat; OC=ovarian cancer; PFS=progression-free survival; Q3W=every 3 weeks; sBRCA1/2=somatic BRCA1/2; tBRCA=tumor BRCA.
References: 1. LYNPARZA® (olaparib) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020. 2. Zejula® (niraparib) [prescribing information]. Waltham, MA: TESARO, Inc.; 2020. 3. Rubraca® (rucaparib) [package insert]. Boulder, CO: Clovis Oncology, Inc.; 2020. 4. Talzenna® (talazoparib) [prescribing information]. New York, NY: Pfizer, Inc.; 2020. 5. Ray-Coquard I, Pautier P, Pignata S, et al. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N Engl J Med. 2019;381(25):2416-2428. 6. Ray-Coquard I, Pautier P, Pignata S, et al. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. Supplementary Appendix. N Engl J Med. 2019;381(25):2416-2428. 7. Ray-Coquard I, Pautier P, Pignata S, et al. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. PAOLA-1 Protocol. N Engl J Med. 2019;381(25):2416-2428. 8. Ray-Coquard I, Pautier P, Pignata S, et al. Phase III PAOLA-1/ENGOT-ov25: maintenance olaparib with bevacizumab in patients with newly diagnosed, advanced ovarian cancer treated with platinum-based chemotherapy and bevacizumab as standard of care. Poster presented at: ESMO 2019; September 27-October 1, 2019; Barcelona, Spain. 9. Konstantinopoulos PA, Ceccaldi R, Shapiro GI, D’Andrea AD. Homologous recombination deficiency: exploiting the fundamental vulnerability of ovarian cancer. Cancer Discov. 2015;5(11):1137-1154. 10. Frey MK, Pothuri B. Homologous recombination deficiency (HRD) testing in ovarian cancer clinical practice: a review of the literature. Gynecol Oncol Res Pract. 2017;4:4. 11. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-674. 12. Myriad myChoice® CDx. Technical Information. Myriad Genetic Laboratories, Inc. Accessed April 12, 2020. https‌:‌/‌/‌bit.ly‌/‌myChoiceCDxSpecs 13. Pennington KP, Walsh T, Harrell MI, et al. Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas. Clin Cancer Res. 2014;20(3):764-775. 14. Data on File, US-35985. AstraZeneca Pharmaceuticals LP. 15. FoundationOne® CDx. Technical Information. Foundation Medicine, Inc. Accessed April 12, 2020. ‌h‌t‌t‌p‌s‌:‌/‌/‌a‌s‌s‌e‌t‌s‌.‌c‌t‌f‌a‌s‌s‌e‌t‌s‌.‌n‌e‌t‌/‌v‌h‌r‌i‌b‌v‌1‌2‌l‌m‌n‌e‌/‌6‌R‌t‌6‌c‌s‌m‌C‌P‌u‌a‌g‌u‌u‌q‌m‌g‌i‌2‌i‌Y‌8‌/‌6‌2‌9‌b‌a‌4‌e‌5‌c‌7‌d‌9‌a‌3‌b‌d‌1‌f‌1‌f‌6‌6‌6‌0‌8‌5‌e‌1‌e‌4‌b‌1‌/‌F‌o‌u‌n‌d‌a‌t‌i‌o‌n‌O‌n‌e‌ _‌C‌D‌x‌_‌L‌a‌b‌e‌l‌_‌T‌e‌c‌h‌n‌i‌c‌a‌l‌_‌I‌n‌f‌o‌.‌p‌d‌f 16. Myriad Genetics. About genetic testing. Accessed April 12, 2020. https‌:‌/‌/‌myriad‌.‌com‌/‌healthcare-professionals‌/‌about-genetic-testing‌/‌overview 17. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines® ) for Ovarian Cancer V.1.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed March 11, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org.
Important Safety Information Prescribing Information
LYNPARZA
LYNPARZA is a registered trademark of the AstraZeneca group of companies.
This product information is intended for US healthcare professionals only.
©2020 AstraZeneca. All rights reserved.
US-43935 Last Updated 8/20
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