To Help Inform Eligibility for First-Line Maintenance Treatment With LYNPARZA

TEST ALL WOMEN WITH ADVANCED OVARIAN CANCER FOR BRCA MUTATIONS1

TUMOR TESTING AT DIAGNOSIS MAY IDENTIFY ~50% MORE WOMEN WITH A BRCAm THAN GERMLINE TESTING ALONE2-5

Nearly 1 in 4 women with advanced ovarian cancer has a BRCAm and may be eligible for first-line maintenance therapy with LYNPARZA.1,4,5

BRCA mutations

BRCAm DETECTION3

  • Identifies both somatic (acquired) and germline (inherited) mutations*
  • Cannot determine if the mutation is germline (inherited)
  • Identifies only germline (inherited) mutations
  • Consult with genetic counselor recommended

To help maximize BRCAm detection, consider ordering both a tumor test and a germline test for all appropriate patients with ovarian cancer.

Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.1

DETECT AT DIAGNOSIS—TEST TUMORS FOR BRCA MUTATIONS AT FIRST TISSUE COLLECTION

Test all women with advanced ovarian cancer for a BRCA mutation at first tumor tissue collection (either at a biopsy or surgical cytoreduction) for timely (~2 weeks) identification of germline and somatic BRCA mutations.2

sBRCA or gBRCA mutations
  • If found to have a BRCAm, consult with genetic counselor for germline testing
  • Primary treatment should not be delayed for a genetic counseling referral7†

TEST FOR BRCA MUTATIONS WITH AN FDA-APPROVED COMPANION DIAGNOSTIC FOR LYNPARZA1

Foundation Medicine Tumor Testing

To order, visit: foundationmedicine.com

Email: client.services@foundationmedicine.com

Call: 1-888-988-3639

To order, visit: myriad.com

Email: cscomments@myriad.com

Call: 1-800-4-MYRIAD

For more information about FDA-approved companion diagnostics for LYNPARZA, visit:
fda.gov/companiondiagnostics1

NCCN Clinical Practice Guidelines In Oncology (NCCN Guidelines®) recommendations for olaparib (LYNPARZA)7

Olaparib (LYNPARZA) is now recommended in the NCCN Guidelines® as an option for maintenance therapy for advanced ovarian cancer following surgery and a complete or partial response to first-line platinum-based chemotherapy in women with a germline or somatic BRCA1/2 mutation.

  • Category 1 recommendation for patients with gBRCAm advanced ovarian cancer and
    Category 2A§ recommendation for patients with sBRCAm advanced ovarian cancer7

NCCN Guidelines® recommendations for BRCA testing9

  • Consider BRCA testing for all women with a personal history of ovarian carcinoma

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.

*Tumor testing cannot distinguish between mutation types.

Recommended for patients with suspected or confirmed epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer.7

Category 1: Based upon high-level evidence, there is uniform (majority panel vote of at least 85% required) NCCN consensus that the intervention is appropriate.7

§Category 2A: Based upon lower-level evidence, there is uniform (majority panel vote of at least 85% required) NCCN consensus that the intervention is appropriate.7

BRCAm=BRCA mutation; gBRCAm=germline BRCA-mutated; NCCN=National Comprehensive Cancer Network®; sBRCAm=somatic BRCA-mutated.

FoundationOne® CDx is a registered trademark of Foundation Medicine, Inc. Myriad BRACAnalysis CDx® is a registered trademark of Myriad Genetics, Inc.

 

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.

Maintenance Recurrent Ovarian Cancer

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.

Advanced gBRCAm Ovarian Cancer

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—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—Maintenance Recurrent Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients in clinical trials of LYNPARZA in the maintenance setting for SOLO-2 were: 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%), decreased appetite (21%) and dyspepsia (20%).

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/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%), mean corpuscular volume elevation (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 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 adjustment to the starting dose is necessary in patients with mild renal impairment (CLcr=51-80 mL/min), but patients should be monitored closely for toxicity. 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).

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