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