Reporting an Indian multicentric community oncology practice’s observation on patterns of homologous recombinant deficiency across various solid cancers evaluated through tumor-DNA-based NGS.

e15066 Background: Homologous recombinant deficiency(HRD) is being evaluated across various solid organ malignancies to assess not just the underlying biological behavior of the cancer but also for potential response to PARP inhibitors. HRD status is assessed by measuring mutations in genes involved in the HRR (Homologous Recombinant Repair) pathway along with other genomic aberrations across the tumor genome like Loss of Heterozygosity (LOH), Telomeric Allelic Instability (TAI) and Large Scale Transitions (LST).We compare here overall HRD scores and their sensitivity and specificity to HRR v/s HRR + LOH, TAI, and LST in an attempt to study the prevalence and pattern of HRD scoring and response to PARPi. Methods: The retrospective data of cancer patients who have undertaken the aforementioned test were evaluated to analyze the patterns of HRD. Responses of a limited subset of patients who received PARP inhibitors were also assessed. Results: A total of 101 patients were evaluated from a community oncology practice over the last 1 year who underwent HRD testing of which 58.4% were female and 41.5% were male. 27.7% of patients were therapy-naive of which 67.8% were stage IV, 28.5% were stage III, and 3.5% were stage I/II while 72.2% were pre-treated and mostly ( > 90%) of advanced stage. The most common cancer types that were tested were Gynaecological cancers (20.7%), followed by Pancreatobiliary (18.8%), Lung (13.8%), Genitourinary (13.8%), and other solid cancers (32.4%). Limited-HRD testing based on small panel HRR genes was performed on 9.9% (10/101) while Comprehensive-HRD (including HRR genes, LOH, TAI, and LST) was performed on 90% (91/101). The sensitivity and specificity of Limited-HRD were 43.75% (with 95% CI 26.36% to 62.34%) and 69.46% (with 95% CI 56.13% to 80.81%) showing an accuracy of 60.44% (with 95% CI 49.64% to 70.54%). Comprehensive-HRD analysis showed a sensitivity of 78.12% (60.03% to 90.72%) and specificity of 67.80% (54.36% to 79.38%) with increased accuracy of 71.43% (with 95% CI 49.64% to 7.54%) as compared to Limited-HRD. PARPi were used in 8.9% (9/101) of patients for organ types- Ovary (44.4%), Prostate (33.3%), Stomach (11.1%), and Lung (11.1%) with a clinical benefit rate of 66.6%. It is also reported that in 3% of cases, BRCA1 mutation was detected however, the comprehensive-HRD score was found low. Conclusions: Predictive sensitivity and accuracy improved with Comprehensive-HRD analysis, thereby reflecting the power of LOH, TAI, and LST in the true identification of both positive and negative cases thus expanding the usage of PARPi in deserving patients.