Clinical outcomes and cost associated with HRD biomarker guided first line maintenance therapy in advanced ovarian cancer

Abstract

<h3>Objectives:</h3> Olaparib is approved as a first line (1L) maintenance (mtx) option, as monotherapy for <i>BRCA</i> mutated (BRCAm) ovarian cancer (OC) and in combination with bevacizumab (Bev) for homologous recombination deficient (HRD) OC. Niraparib monotherapy is approved as 1L mtx irrespective of BRCA/HRD status. Despite its broad approval, niraparib demonstrated relatively shorter progression free survival (PFS) gains outside of an HRD test positive population in the PRIMA trial. Given the recent PARPi data in frontline mtx and the cost of HRD testing beyond standard of care g<i>BRCA</i> testing, there is debate over using an HRD biomarker guided (BMG) or non-biomarker guided (NBMG) approach to prescribing 1L mtx. The objective of this model is to compare the PFS and costs per month of PFS between: (1) BMG 1L mtx approach which restricts the prescribing of 1L mtx PARPi and PARPi combination based on Myriad myChoice results vs (2) NBMG PARPi mtx for all approach. <h3>Methods:</h3> This model is a parametric Markov model for a cohort of 100 newly diagnosed stage 3/4 OC patients (pts) prescribed 1L mtx according to HRD BMG and NBMG approaches. The model focuses on maintenance after first line treatment and evaluates costs and PFS after first line chemotherapy. To focus on the impact of testing, drugs are treated as classes. Treatment costs include 1L mtx PARP inhibitor (PARPi), Bev, and PARPi + Bev, subsequent therapy, management of adverse events, and administration costs over 60 months. PFS is estimated by applying an exponential curve to adjusted trial data. The BMG pt group undergoes HRD tumor testing and has a test positive (HRD+) rate of 47% (20% BRCAm, 27% non-BRCAm). Germline <i>BRCA</i>m testing cost is not included as it is assumed to be the standard of care and equally conducted in both groups. An estimated 65% are eligible for a PARPi (received and responded to 1L platinum chemotherapy). Calculations for the BMG PARPi eligible group assume all HRD+ pts receive PARPi + Bev and 30% of HRD test negative pts receive Bev (70% receive routine surveillance). The model assumes all pts in the NBMG group receive a PARPi. <h3>Results:</h3> In the BMG group 31 pts receive PARPi + Bev mtx and in the NBMG arm 65 pts receive PARPi mtx. The 31 BMG PARPi + Bev pts averaged 36.6 months of 1L PFS compared to 26.3 months in the 65 NBMG PARPi pts. The overall 1L PFS for the total cohorts were similar but slightly favored the BMG approach (1715.4 vs 1711.7 months). Over a 60 month horizon, the BMG approach was $1,002 less per month of 1L PFS gained ($15,475 vs. $16,477). HRD biomarker testing represented 1.5% of the total costs for the cohort. <h3>Conclusions:</h3> Despite initial testing costs, this model projects that use of an HRD BMG approach with PARPi + bev may minimize long-term costs and afford at least similar, if not greater, 1L PFS compared to an approach which omits HRD tumor testing and prescribes PARPi to all-comers.