4536 - Cascade BRCA Germline Mutation (BGM) Testing of women with Breast (BC) or Epithelial Ovarian Cancer( EOC) and their families with subsequent Risk Reducing Surgery(RRS): A Canadian Economics Model

Background

Targeted prevention by RRS in mutation carriers ( first test the index case with BC or EOC and , if positive, their family ) saves lives. BGMs rates: EOC (12 - 18%), BC ( 1- 5%). BRCA1 carriers have a 35 - 60% EOC risk and 65% for BC; BRCA2 12- 25% and 45% respectively. RRS prevents 80-90%. Does this also represent value for money compared to no prevention with treatment upon occurrence?

Methods

A patient level simulation was used: 50 yr time frame and all cause mortality endpoint. Assumptions: 1) all index cases and female family had BGM 2) all unaffected carriers had RRS – bilateral salpingo-oopherectomy (RRBSO) and bilateral mastectomy (RRM) 3) 26,316 and 2786 BC and EOC per year in Canada 4) BGM rate in EOC 12.6% ( 61.6% BRCA1; 38.4% BRCA 2) ; 4.7% in BC ( 51% BRCA1, 49% BRCA2) 5) test 1⁰ relatives if index case positive ( 50% risk) and test 2⁰ if 1⁰ positive (25% risk) 6) prevention by RRS for EOC is 84% and 90% for BC 7) Standard therapy cures 50% EOC and 90% of BC. Costs: BRCA testing/counselling $1000; RRBSO $9080; RRM $5833; EOC chemotherapy $34,412 / year and BC one time cost $23,796; palliative care costs EOC $14,687, BC $29,993. Cancer -related utilities 0.5 to 0.72 for EOC and BC 0.71 to 0.77 .

Results

29,102 index cases (1yr). 1668 had BRCA mutation as did 1593 1⁰ and 275 2⁰0 relatives. Cases prevented: EOC 270 and BC 426. Total 50 year cost for testing/RRS cohort was $255 million and $285 million in the control cohort. ICER ( incremental cost effectiveness ratio) was - $7901 per quality adjusted life year ( dominant). Sensitivity analyses showed less cost effective ICER as testing /RRS rates fell. At real world rates e.g. 44% RRBSO and 21% RRM, ICER was $20,176. All probabilistic sensitivity analyses remained in the cost-effective quadrant (North American ICER < $100,000).

Conclusions

Targeting the high risk for RRS saves lives and is cost-effective under a wide range of inputs. These data are conservative as excluded are the indirect costs of treatment i.e. family/societal costs and increasing drug costs. Healthcare systems must ensure as close to 100% BGM / RRS rates as this saves the most lives,is cost efficacious and also saves money.

Clinical trial identification

Legal entity responsible for the study

Paul Hoskins.

Funding

AstraZeneca.

Editorial Acknowledgement

not applicable

Disclosure

P. Hoskins: Advisory boards: AstraZeneca, Roche, Pfizer, Purdue. A. Ecclestone: Funding to do analysis for this paper: AstraZeneca. M. Hurry, M. Dyer: Employee: AstraZeneca.