199P - Association of homologous recombination deficiency status with outcomes for ovarian cancer patients treated with olaparib, and exploration of other biomarkers of relapse and survival

Background

The homologous recombination deficiency (HRD) status has displayed the good predictive value for the survival and efficacy of ovarian cancer patients (OCs) received Olaparib in first-line therapy or after platinum-sensitive relapse (PSR). However, the efficacy and survival of Olaparib in some patients is dismal, in which the effective molecular biomarkers remain to be explored.

Methods

Total 60 patients (January 2016 to March 2021) received Olaparib (300 mg, BID) with or without Bevacizumab (7.5-15 mg/kg, once every 21 days) (PSR OCs, N=19; Non-PSR OCs, N = 41), and undergo HRD test by AmoyDx® HRD Focus Panel (HRD-positive, GSS score ≥ 50 or BRCA1/2 mutated). Through genomics and transcriptomics-based data, underlying mechanisms associated with efficacy and prognosis of 24 OCs with Olaparib treatment was identified. The primary endpoint was progression-free survival (long-PFS: > 12 months, short-PFS: ≤ 12 months).

Results

HRD status was determined in 60 OCs with received Olaparib. HRD was an independent prognosis factor (p = 0.029) according to the multivariate Cox regression analysis, and HRD-positive was correlated with longer PFS (p = 0.0064), especially for patients received Olaparib first-line therapy. High ICOSLG expression was associated with shorter PFS (p = 0.0073, AUC = 0.847). High co-expression of ICOSLG and DLX2, predicted higher recurrence rate (p = 0.01), and was verified as a predictive factor (ICOSLG^high & DLX2^high AUC = 0.81). Enrichment ratio of mast cells (MCs) was higher in the short-PFS group than in the long-PFS group (p = 0.053) with critical significance. A low percentage of dendritic cells (DCs) was significantly related to high recurrence rate (p = 0.033). High MCs and low DCs ratio signify an immunosuppressive microenvironment.

Conclusions

In the study, we confirmed that HRD-positive patients can benefit from Olaparib therapy, and have a good prognosis. ICOSLG^high and ICOSLG^high & DLX2^high, as potential biomarkers of survival and Olaparib efficacy, may help to better identify patients who will benefit most from Olaparib treatment and require further validation in clinical studies.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.