Locus-Specific Loss Of Heterozygosity (Loh) In Brca1/2 Mutated (Mbrca) Ovarian Tumors From The Solo2 (Nct01874353) And Study 19 (Nct00753545) Clinical Trials.

5563Background: The PARP inhibitor olaparib is approved in the US for patients with mBRCA (germline) advanced ovarian cancer, and in the EU for platinum-sensitive relapsed mBRCA (germline or somatic) ovarian cancer. A recent study reported retention of a normal allele in 7% of germline BRCA1 mutant ovarian tumors and 16% of germline BRCA2 ovarian tumors, and suggested that absence of locus-specific LOH may be a biomarker of primary resistance to DNA damaging agents (Maxwell KN et al, Nature Commun. 2017;22:319). Methods: mBRCA tumors were identified from two trials with patients with platinum sensitive relapsed ovarian cancer: SOLO2 (NCT01874353), Study 19 (NCT00753545). Analysis was performed on tissue obtained at the time of diagnosis. LOH status was assigned using a genomic instability algorithm, and confirmed via human review. Both processes evaluated relative read count and allele dosage data from 54,000 independent SNPs. Results: 210 mBRCA tumors (144 BRCA1, 66 BRCA2) were identified in the SOLO2 co...