Prevalence, genomic landscape, and outcomes of HRD and HRR alterations in solid tumors: Real-world data from western India.

Abstract

e15207 Background: HRD and HRR alterations are key predictive and prognostic biomarkers in solid tumors, guiding targeted therapy selection. Limited Indian real-world data exist on their prevalence, genomic profile, and outcomes across cancer types. Methods: The retrospective data of cancer patients who have undertaken the aforementioned test from Jan 2018 to July 2025 were evaluated. Treatment patterns, PARP inhibitor use, and survival outcomes were analyzed; mOS was estimated using Kaplan–Meier and compared by log-rank test. Results: A total of 566 patients underwent HRD and HRR testing with a median age of 61 years (IQR 52–70) and the most common cancer type tested were gynecological (29.3%,n = 166), breast (23.5%,n = 133). Next Generation Sequencing-based genomic profiling revealed HRD positivity in 26.7% (n = 151), with the highest prevalence in gynecological cancers (39.1%), followed by breast (15.9%), genitourinary and hepatobiliary (8.6% each). Among positive cases, 67 were HRR-positive and 84 were HRD-positive, with comprehensive LOH, TAI, and LST scoring available for 81 of the HRD-positive patients and TAI was the predominant determinant of HRD positivity. While the most common HRR genes alteration detected were BRCA1 (17.3%), TP53 (15.8%), and ATM (11.4%). Among HRD-positive cases, 64.9% (98/151) had positive mutation, most commonly involving BRCA in 29.6%, TP53 in 27.6% and 5.1% exhibiting concurrent BRCA and TP53 mutations however 35.1% had HRD positivity without any mutation based on genomic scar score. PARP inhibitors were used in 30.5% of patients, most frequently olaparib (82.6%), with an overall response rate 69.8%. Among HRD-positive patients, mOS was not reached for BRCA-mutated cases compared to 36.8 months for non-BRCA mutated cases (p = 0.012). Conclusions: This study reinforces the pivotal role of universal HRD testing in informing biomarker-driven therapeutics, maximizing survival gains, and narrowing gaps in implementing precision cancer care. HRD positivity with BRCA positivity have better response rate as compared to HRD with non BRCA mutated patients.