998PD - Analysis of tumour samples from SOLO1: Frequency of BRCA specific loss of heterozygosity (LOH) and progression-free survival (PFS) according to homologous recombination repair deficiency (HRD)-LOH score

In SOLO1 (NCT01844986; GOG-3004), maintenance olaparib significantly improved PFS vs placebo (HR 0.30; 95% CI 0.23–0.41; Moore et al. NEJM 2018) in patients (pts) with newly diagnosed advanced ovarian cancer and a BRCA1 and/or BRCA2 mutation (BRCAm), who were in clinical complete or partial response...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Annals of oncology 2019-10, Vol.30, p.v407-v407
Hauptverfasser: Gourley, C., Brown, J.S., Lai, Z., Lao-Sirieix, P., Elks, C.E., McGarvey, H., French, T., Milenkova, T., Bloomfield, R., Rowe, P., Hodgson, D., Barrett, J.C., Moore, K., DiSilvestro, P., Harrington, E.A.
Format: Artikel
Sprache:eng
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:In SOLO1 (NCT01844986; GOG-3004), maintenance olaparib significantly improved PFS vs placebo (HR 0.30; 95% CI 0.23–0.41; Moore et al. NEJM 2018) in patients (pts) with newly diagnosed advanced ovarian cancer and a BRCA1 and/or BRCA2 mutation (BRCAm), who were in clinical complete or partial response after first line treatment, which includes surgery and platinum-based chemotherapy. We analyzed BRCA LOH and PFS by genome-wide HRD-LOH score in SOLO1. Archival diagnostic tumour samples from 341/391 pts from SOLO1 were analysed using the Foundation Medicine F1CDx clinical trial assay. Tumour BRCA1 and BRCA2 LOH was determined using the SGZ-computational method (Sun et al. 2018). HRD-LOH score (genomic instability scar) was also generated and compared with PFS using a Cox Proportional Hazards model. Of evaluable tumours, 99% (275/277) had BRCA1 or BRCA2 LOH, including 2 pts with a somatic BRCAm. Two germline BRCA2m tumours lacked LOH. 283/341 (83.0%) tumours sequenced at FMI were evaluable for HRDLOH score. Using established cut-offs of 14 and 16 (Swisher et al. 2017); 84% (237/283) and 77% (218/283), respectively, would be considered HRD-LOH high. BRCAm pts with HRD-LOH scores
ISSN:0923-7534
1569-8041
DOI:10.1093/annonc/mdz250.006