A closer look at BRCA mutations in advanced ovarian cancer

Approximately 1 in 4 women with ovarian cancer may have a BRCA mutation1

Key differences between germline and somatic BRCA mutations1-4

BRCA Mutations Germline Somatic
Prevalence 18% 7%
Origin of mutation Inherited Acquired
Location of mutation Found in all cells in the body Found only in tumor cells

Testing of BRCA mutations

INDICATION

Rubraca (rucaparib) is indicated as monotherapy for the treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with two or more chemotherapies. Select patients for therapy based on an FDA-approved companion diagnostic for Rubraca.

This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Testing tumor DNA for BRCA mutations may identify patients who may benefit from PARP inhibition1,2,5,6

  • In clinical trials of Rubraca, BRCA mutation status was determined using the FoundationFocus™ CDxBRCA test
  • Archived tumor tissue can be used to test for both germline and somatic mutations

References

1. Pennington KP, Walsh T, Harrell MI, et al. Clin Cancer Res. 2014;20(3):764-775. 2. Robson ME, Bradbury AR, Arun B, et al. J Clin Oncol. 2015;33(31):3660-3667. 3. Hennessy BTJ, Timms KM, Carey MS, et al. J Clin Oncol. 2010;28(22):3570-3576. 4. Petrucelli N, Daly MB, Feldman GL. BRCA1 and BRCA2 hereditary breast and ovarian cancer. 1998 Sep 4 [Updated 2013 Sep 26]. In: Pagon RA, Adam MP, Ardinger HH, et al, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. 5. Mafficini A, Simbolo M, Parisi A, et al. Oncotarget. 2016;7(2):1076-1083. 6. Watkins JA, Irshad S, Grigoriadis A, et al. Breast Cancer Res. 2014;16(3):211.

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SELECT IMPORTANT SAFETY INFORMATION
SELECT IMPORTANT SAFETY INFORMATION

Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) was reported in 2 of 377 (0.5%) patients with ovarian cancer treated with Rubraca. The duration of Rubraca treatment prior to the diagnosis of MDS/AML was 57 days and 539 days. Both patients received prior treatment with platinum and other DNA damaging agents.

AML was reported in 2 (< 1%) patients with ovarian cancer enrolled in a blinded, randomized trial evaluating Rubraca versus placebo. One case of AML was fatal. The duration of treatment prior to the diagnosis of AML was 107 days and 427 days. Both patients had received prior treatment with platinum and other DNA damaging agents.

Do not start Rubraca until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1).

Monitor complete blood count testing at baseline and monthly thereafter. For prolonged hematological toxicities, interrupt Rubraca and monitor blood counts 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. If MDS/AML is confirmed, discontinue Rubraca.

Based on its mechanism of action and findings from animal studies, Rubraca can cause fetal harm when administered to a pregnant woman. Apprise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of Rubraca.

Most common adverse reactions (≥ 20%; Grade 1-4) were nausea (77%), asthenia/fatigue (77%), vomiting (46%), anemia (44%), constipation (40%), dysgeusia (39%), decreased appetite (39%), diarrhea (34%), abdominal pain (32%), dyspnea (21%), and thrombocytopenia (21%).

Most common laboratory abnormalities (≥ 35%; Grade 1-4) were increase in creatinine (92%), increase in alanine aminotransferase (ALT) (74%), increase in aspartate aminotransferase (AST) (73%), decrease in hemoglobin (67%), decrease in lymphocytes (45%), increase in cholesterol (40%), decrease in platelets (39%), and decrease in absolute neutrophil count (35%).

Because of the potential for serious adverse reactions in breast-fed infants from Rubraca, advise lactating women not to breastfeed during treatment with Rubraca and for 2 weeks after the final dose.

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Clovis Oncology, Inc. at 1-844-258-7662.

Please see full Prescribing Information for additional Important Safety Information.