Understanding testing for and treatment of homologous recombination repair (HRR)-mutated metastatic castrate-resistant prostate cancer (mCRPC): A quality initiative by Integra Connect PrecisionQ.

Abstract

581 Background: In May of 2020, the approval of two Poly (ADP-ribose) polymerase inhibitors (PARPi) changed the landscape for treatment among patients (pts) with HRR mutations (HRRm) in mCRPC. The University of Pittsburgh Medical Center (UPMC) conducted a Quality Initiative (QI) with Integra Connect PrecisionQ to assess the rates of HRR testing, HRR positivity, and PARPi use in HRRm patients with mCRPC. This QI included clinical interventions to optimize testing and treatment in these patients. We aim to show the improvement in HRR testing and rates of treatment with PARPi after implementation of the QI in patients with HRRm mCRPC at UPMC. Methods: Using the de-identified Integra Connect PrecisionQ database, 223 UPMC pts with mCRPC were selected by medical chart curation as the baseline group. Patients in this group had received treatment between 5/1/2020 to 9/30/2021 and were confirmed as mCRPC. The baseline data was reviewed with UPMC clinical leadership, discussed at a physician roundtable, and shared among providers. Post-baseline, we evaluated 152 mCRPC pts who started a new line of therapy between 1/1/2022 to 12/31/2022 to assess HRR testing rates and use of PARPi in eligible mCRPC pts. The presence of one or more HRR genes was used to determine testing rates. Descriptive analyses were performed and a two-proportion z-test was used for comparisons of HRR testing in patients with mCRPC and treatment with a PARPi in HRRm mCRPC pts. Results: The average age at diagnosis was 67 years, 47% of patients had a Gleason score of > = 8, and 62% were stage IV. The rate of HRR testing at baseline was 52% (116 of 223). The results post-baseline and intervention showed an increase in HRR testing to 69% (105 of 152) of mCRPC patients who started a new line of therapy in 2022 (p < 0.01). At baseline, 60% (21 of 35) of HRRm pts were treated with a PARPi after prior NHA treatment, compared to 68% (19 of 28) post-baseline and intervention (p > 0.05). Among all HRR mCRPC tested pts, there was a 30.9% (84/272) positivity rate, of which 11.4% were BRCA1/2 positive (30/262) and 10.5% were ATM positive (26/247). Not all patients tested for HRR were tested for all genes. Conclusions: This Quality Initiative to improve testing and identification of HRR mutations in patients with mCRPC led to a 33% relative increase in HRR testing, demonstrating how QI programs can transform care and move the field toward individualized, precision medicine.