773P - Real-world results of homologous recombination deficiency testing: Comparison between two methods on 2,655 ovarian cancer patients in Spain

Background

Homologous Recombination Deficiency (HRD) is assessed by detection of mutations in BRCA1/2 genes (BRCAm) and/or genomic instability score (GIS+). In ovarian cancer, HRD has become an important biomarker to stratify patients for appropriate clinical management and treatment. Myriad myChoice CDX Plus is currently the gold standard for assessing HRD on tumor samples. There is an increasing interest in transitioning into inhouse HRD assays that fulfill analytical concordance and, also, demonstrate clinical validation. Sophia DDM Dx HRD solution is one of the alternatives, which has reached an overall percent agreement of 93% with Myriad, demonstrating also clinical validation in PAOLA-1 trial. In this study, we present the real-world results of HRD testing in Spain.

Methods

Phase 1 (Apr2021-Jun22), consisted in the analysis of 1322 cases from 90 centers, using Myriad myChoice. Phase 2 (Jul2022-Dec22) included 1333 cases from 135 centers, analyzed with Sophia HRD solution in 4 academic centers, after an internal validation.

Results

Phase 1 reported 47% BRCAwt/GIS-, 24% BRCAwt/GIS⁺, 14% BRCAm (BRCAm/GIS- y BRCAm/GIS+), and 15% inconclusive cases using myChoice. In phase 2, Sophia HRD identified 47% BRCAwt GIS-, 25% BRCAwt/GIS+, 15% BRCAm, and 13% inconclusive cases. The distribution of HRP (range 42.4-50%) and HRD (range 35.7- 40.7%) cases was similar among the reference centers. In addition to GIS and BRCA1/2, Sophia reported CCNE1 amplification (5.3%), as well as mutations in BRIP1 (2.4%), RAD51C (1.1%), RAD51D (1.2%) and PALB2 (1.9%). As expected, CCNE1 amplification was more frequent in HRP (86.5%) than HRD (13.5%).

Conclusions

The results obtained from a cohort of 2655 ovarian cancer samples by two different methods, Myriad myChoice and Sophia HRD, confirm the analytical concordance between HRD assays. Percentages of BRCAwt/GIS-, BRCAwt/GIS+, BRCAm, and invalid cases were almost identical. In conclusion, Sophia DDM^TM Dx HRD solution shows a high interlaboratory agreement, providing clinically relevant molecular information, and improving the interaction between referral and reference centers.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Federico Rojo.

Funding

AstraZeneca.

Disclosure

M. Orellana: Financial Interests, Personal, Member: AstraZeneca. M. Lencina: Financial Interests, Personal, Other: AstraZeneca. X. Matias-Guiu: Financial Interests, Personal, Advisory Board: AstraZeneca, Amgen, Lilly, GSK, Janssen; Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK, Clovis; Non-Financial Interests, Other, Consultancy: AstraZeneca. F. Rojo: Financial Interests, Personal, Advisory Board: Roche, MSD, BMS, Novartis, AstraZeneca, Daiichi Sankyo, GSK; Financial Interests, Personal, Invited Speaker: Merck. All other authors have declared no conflicts of interest.