Test for BRCA1/2 and other HRR mutations* to help identify appropriate patients with mCRPC for LYNPARZA combination therapy or monotherapy1

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend testing for BRCA1/2 and other HRR mutations for patients with mCRPC2

Use FDA-approved companion diagnostics to help determine eligibility for olaparib (LYNPARZA) in mCRPC.1

WHO TO TEST AND WHEN TO TEST1-6:

Germline testing is recommended in patients with a personal history of prostate cancer in the following scenarios: Patients with metastatic, regional (node positive), very high-risk localized, or high-risk localized prostate cancer.

Tumor testing: Metastatic prostate cancer (recommended); regional prostate cancer (consider).

Type of Test Mutation Detected
Tumor Tissue
FoundationOne®CDx†		 BRCA1/2 and other HRRm*
Germline and Somatic
Plasma ctDNA Testing
FoundationOne®Liquid CDx†		 BRCA1/2 and ATM
Germline and Somatic
Germline Blood Testing
BRACAnalysis CDx®		 BRCA1/2
Germline Only

Both somatic and germline BRCA mutations may have prognostic and/or treatment implications in mCRPC. Germline BRCA mutations may also inform genetic risk for patients and their families.

Where testing fails, the tissue sample is unavailable/insufficient, or when germline testing is negative, consider using an alternative test, if available.

  • *Other HRR gene mutations detected: ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, and RAD54L.
  • †Detects both somatic and germline alterations but does not distinguish between the two on reports.
  • FoundationOne® is a registered trademark of Foundation Medicine, Inc. BRACAnalysis CDx® is a registered trademark of Myriad Genetics, Inc.

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.

See additional companion diagnostic information below.

WHY TEST:

Combination therapy (PROpel trial): BRCA1/2 gene profile in patients tested (n=796)1,7-9

Among patients with mCRPC who were tested for BRCA1/2 mutations* based on aggregate samples in the PROpel study:

~11%

of patients with mCRPC in the PROpel trial had a BRCA1/2 mutation

mCRPC Testing PROpel Trial Pie Chart

In PROpel, BRCA gene mutation (BRCAm) status was assessed after randomization and before primary analysis by both
NGS-based tumor tissue and ctDNA tests. BRCAm classification criteria in line with the FDA-approved assays were used to determine the deleterious and suspected deleterious somatic or germline mutation status of patients.

  • *BRCA mutations were identified based on HRR testing using a ctDNA-based test (FoundationOne® Liquid CDx) or a tumor tissue test (FoundationOne® CDx).

Monotherapy (PROfound trial): HRR gene profile in patients with biomarker status reported (n=2792)1,10,11

Among patients with mCRPC who were prospectively screened and had biomarker status reported for BRCA1/2 and other HRR gene alterations† in PROfound:

~28%

of patients with mCRPC in the PROfound trial
had an HRR gene mutation, such as a BRCA1/2 or ATM mutation

mCRPC Testing PROfound Trial Pie Chart

In PROfound, patients with HRR gene mutations were identified by tissue-based testing using the Foundation Medicine FoundationOne® clinical trial HRR assay performed at a central laboratory. Determination of deleterious or suspected deleterious somatic or germline HRR mutation status in line with the FDA-approved mutation classification and testing criteria for the Foundation Medicine F1CDx tissue-based assay and assessment of the germline BRCA status using the Myriad BRACAnalysis CDx® blood-based assay was performed retrospectively.

  • †HRR gene mutations (BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, and/or RAD54L) were identified by tissue-based testing using the Foundation Medicine FoundationOne® clinical trial HRR assay performed at a central laboratory. No patients were enrolled who had mutations in 2 of the 15 prespecified genes: FANCL and RAD51C.
  • ‡Although patients with PPP2R2A gene mutations were enrolled in the PROfound trial, LYNPARZA monotherapy is not indicated for the treatment of patients with this gene mutation due to an unfavorable risk-benefit.
LYNPARZA Testing

HOW TO TEST:

Using an FDA-approved companion diagnostic for LYNPARZA1,4-6,10

TEST

MUTATIONS DETECTED

FOUNDATIONONE® CDx Logo

Tissue biopsy test

Mutations detected

BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, RAD54L

  • •Detects both somatic and germline alterations but does not distinguish between the two on reports
  • •Requires archived or recent biopsy tissue from primary or metastatic tumor
  • •Uses DNA isolated from formalin-fixed, paraffin-embedded (FFPE) tumor tissue specimens

Visit FoundationMedicine.com/order
to order test kits, or call 1-888-988-3639 1-888-988-3639

FOUNDATIONONE® LIQUID CDx Logo

Plasma ctDNA test

Mutations detected

BRCA1, BRCA2, ATM

  • •Detects both somatic and germline alterations but does not distinguish between the two on reports
  • •Requires peripheral whole blood
  • •~80% of patients (n=111/139) identified to have alterations in BRCA1, BRCA2, and ATM through a tissue biopsy test were also confirmed/identified through a plasma ctDNA test (95% CI: 72.2%–86.2%)*
  • *Based on a clinical bridging study using screening
    (ie, pre-olaparib treatment) plasma samples from Cohort A of the PROfound trial.

Visit FoundationMedicine.com/order
to order test kits, or call 1-888-988-3639 1-888-988-3639

BRACAnalysis CDx® Logo

Blood test

Mutations detected

gBRCA1, gBRCA2

  • •Detects only germline alterations
  • •Requires blood sample

Visit BRACAnalysisCDx.com/order-test
to order test kits, or call 1-800-4-MYRIAD 1-800-4-MYRIAD

Where testing fails or tissue sample is unavailable/insufficient, or when germline testing is negative, consider using an alternative test, if available.1

FoundationOne® and BRACAnalysis CDx® are not registered trademarks of the AstraZeneca group of companies or Merck, Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., FoundationOne® CDx, FoundationOne® Liquid CDx, and BRACAnalysis CDx® are not products of AstraZeneca or Merck, and neither AstraZeneca nor Merck make any warranty or representation regarding these products. Consult CDx label information prior to use: www.F1CDxLabel.com and www.F1LCDxLabel.com or https://s3.amazonaws.com/myriad-web/BRACAnalysisCDxTS.pdf. FoundationOne® is a registered trademark of Foundation Medicine, Inc. BRACAnalysis CDx® is a registered trademark of Myriad Genetics, Inc.