Association between chemotherapy response score (CRS) and tumour homologous recombination deficiency (tHRD) in women with newly diagnosed FIGO stage IIIC/IV high-grade serous ovarian cancer (HGSOC)

BackgroundPathology-defined omental CRS after neoadjuvant chemotherapy (NACT) predicts survival outcomes in women with newly diagnosed FIGO stage IIIC/IV HGSOC. HRD-positive tumours have a superior response to PARPi therapy compared to HRD-negative tumours. We investigated the association between CRS and tHRD to assess CRS as a cost-free, potential biomarker for PARPi efficacy.MethodsEligible women included those with newly diagnosed FIGO stage IIIC/IV HGSOC treated with NACT and tested using Myriad’s myChoice® tHRD assay at The Christie Hospital between April 2021 and December 2023. Univariable and multivariable (MV) Cox proportional hazards models were developed to validate the association between survival outcomes and key clinical factors. The association between CRS3 (no/minimal residual tumour) and tHRD was assessed using the chi-squared test.Results315 women were included in the overall population (median age 67, range 36-91). 89 (28%) had FIGO stage IVB disease and 47 (15%) had a tBRCA1/2 mutation. 197 (63%) received 3-weekly carboplatin-paclitaxel. MV analysis of the overall population showed that undergoing primary cytoreductive surgery (yes vs. no) was prognostic (P<0.01). 200 women underwent delayed primary surgery (DPS) and had a CRS reported (table). Of these, 162 (81%) received 3–4 cycles of NACT and 128 (64%) had complete debulking. MV analysis of the DPS group showed surgical outcome (complete vs. optimal/suboptimal; P<0.01) and CRS (3 vs. 2+1; P=0.015) were prognostic. The chi-squared test showed that HRD-positive tumours were more likely to have CRS3 than HRD-negative tumours (P=0.043). Table: 775P CRS tHRD status PFS / months, median (95% CI) Positive Negative Unknown ∗ 1 18 24 2 14.0 (12.0-NR) 2 42 44 10 14.4 (12.9-17.3) 1+2 60 (67%) 68 (81%) 12 14.3 (13.3-17.3) 3 29 (33%) 16 (19%) 15 26.3 (24.6-NR) ∗Test failed; NR, not reached. ConclusionsWe found an association between tHRD and omental CRS in women with newly diagnosed FIGO stage IIIC/IV HGSOC treated with NACT and DPS. CRS should be evaluated in a prospective study as a biomarker of PARPi efficacy.Legal entity responsible for the studyThe Christie NHS Foundation Trust.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.