Abstract PO2-03-09: Cost-effectiveness analysis of RAD51 functional biomarker for platinum sensitivity in the GeparSixto trial
Authors: Isabel Pimentel, Carles Forné, Alba Llop-Guevara, Misericòrdia Carles-Lavila, Violeta Serra, Montserrat Rué, Judith Balmaña
Journal: Cancer Research (2024)

Abstract Background: Homologous recombination repair deficiency (HRD) has long been recognized as a predictive biomarker for platinum sensitivity and is present in up to 60% of early triple negative breast cancers (TNBC). Different commercial and lab-developed assays to measure HRD are available, but they do not necessarily reflect homologous recombination functionality. Functional HRD, defined by a low score in RAD51 foci, is emerging as an accurate and dynamic biomarker to predict DNA damaging agents’ response. We performed a cost-effectiveness evaluation of the RAD51 test compared to tumor BRCA1/2 mutation (tBRCA1/2) or genomic HRD by Myriad Mychoice® to identify patients sensitive to platinum-based chemotherapy within the GeparSixto trial. Methods: The effectiveness measure was the primary outcome of the GeparSixto study: rate of pathological complete response (pCR), defined as ypT0 ypN0. The pharmacological costs were calculated following treatment protocol of GeparSixto where TNBC patients received neoadjuvant paclitaxel plus Myocet®-nonpegylated liposomal doxorubicin (PM) or PM plus carboplatin (PMCb), both arms including bevacizumab. Bevacizumab was excluded from the cost analysis as it is not administered by standard practice. The cost of a session/stay at the day hospital was added, as well as the cost of the test used, comparing 4 scenarios: All comers (assuming all patients receiving PMCb); RAD51 test (assuming RAD51 ≤10% received PMCb and RAD51 &amp;gt;10% received PM); tBRCA1/2 test (assuming tBRCA1/2 mutated received PMCb and tBRCA1/2 non-mutated received PM) and genomic HRD by Myriad Mychoice® (HRD score ≥42 received PMCb, and HRD score &amp;lt;42 received PM). The available commercial costs were considered for tBRCA1/2 and Myriad Mychoice®, and the VHIO performance cost was considered for the RAD51 test. Parameter uncertainties were assessed by means of one-way and probabilistic sensitivity analyses. Results: All comers total cost was 20,530€ per patient, with associated pCR rate of 54.5%. Functional RAD51 test was associated with a pCR probability of 55.1% with a Δ cost of 198€, as opposed to tBRCA1/2 which presented a pCR rate of 40.1% with a Δ cost of 814€, and genomic HRD with 47% pCR rate and the higher Δ cost of 1,023€ per patient, when compared to all comers. The incremental cost-effectiveness ratio (Δ cost/Δ pCR) was 33,000 for RAD51 test and dominated in both tBRCA1/2 and genomic HRD tests. These results were robust on one way and probabilistic sensitivity analyses. Conclusion: The most efficient scenarios are the functional RAD51 test and all comers. Both tBRCA1/2 and genomic HRD by Myriad Mychoice® scenarios provide worse health outcomes at a higher cost, based on the data of the GeparSixto trial. This study highlights the potential overall benefit of functional HRD biomarkers to predict PARPi sensitivity. Citation Format: Isabel Pimentel, Carles Forné, Alba Llop-Guevara, Misericòrdia Carles-Lavila, Violeta Serra, Montserrat Rué, Judith Balmaña. Cost-effectiveness analysis of RAD51 functional biomarker for platinum sensitivity in the GeparSixto trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-03-09.