Aurore Carrot

Prognostic Value of a Joint K‐PD Model With Tumor Size Dynamics and CA‐125 Kinetics in Recurrent Ovarian Cancer Patients: BOLD Phase II GINECO Study

ABSTRACTIn patients with recurrent advanced ovarian cancer, there is a need for companion tests to guide the development of innovative chemotherapy‐free treatments. The modeled longitudinal CA‐125 ELIMination rate constant K KELIM‐B was a major prognostic factor for progression‐free survival (PFS) and overall survival (OS) in recurrent advanced ovarian cancer patients treated with bevacizumab, olaparib, and durvalumab in the BOLD trial. The objective was to determine if a joint semi‐mechanistic model with tumor size and CA‐125 kinetics would increase KELIM‐B accuracy/prognostic value. The BOLD phase II trial (NCT04015739) investigated the triplet regimen in 74 patients with recurrent platinum‐sensitive/resistant advanced ovarian cancer. Two kinetic‐pharmacodynamic models were developed to fit the data collected during the first 100 treatment days: (1) a CA‐125 longitudinal kinetics model, and (2) a joint model integrating both CA‐125 kinetics and tumor size. The prognostic value of KELIM‐B and KELIM‐joint was assessed using univariate/multivariate analyses (PFS/OS). The modeling of CA‐125 and tumor size dynamics was feasible with adequate quality checks. The prognostic value of the categorical KELIM‐joint, binarized by the median (PFS, HR = 0.29, 95% CI [0.12–0.72]; OS, HR = 0.24, 95% CI [0.08–0.74]), was not clinically different from that of KELIM‐B (PFS, HR = 0.35, 95% CI [0.14–0.84]; OS, HR = 0.34, 95% CI [0.12–0.99]). Interactions between tumor size changes and CA‐125 kinetics could be assessed in the joint model. However, the improvement in prognostic value was not sufficient to justify the higher complexity of the joint model. Assessing early longitudinal CA‐125 kinetics alone remains the best pragmatic strategy for future development.

KELIM score predicts outcome in patients with platinum-resistant/refractory recurrent ovarian cancer

Germline BRCA1/2 status and chemotherapy response score in high-grade serous ovarian cancer

Abstract Background High-grade serous ovarian cancer (HGSOC) can be treated with platinum-based neoadjuvant chemotherapy (NACT) and delayed primary surgery (DPS). Histopathological response to NACT can be assessed using Böhm’s chemotherapy response score (CRS). We investigated whether germline BRCA1/2 (gBRCA1/2) genotype associated with omental CRS phenotype. Methods A retrospective study of patients with newly diagnosed FIGO stage IIIC/IV HGSOC prescribed NACT and tested for gBRCA1/2 pathogenic variants (PVs) between September 2017 and December 2022 at The Christie Hospital. The Cox proportional hazards model evaluated the association between survival and key clinical factors. The chi-square test assessed the association between CRS3 (no/minimal residual tumour) and gBRCA1/2 status. Results Of 586 eligible patients, 393 underwent DPS and had a CRS reported. Independent prognostic factors by multivariable analysis were gBRCA1/2 status (PV versus wild type [WT]), CRS (3 versus 1 + 2), surgical outcome (complete versus optimal/suboptimal) and first-line poly (ADP-ribose) polymerase-1/2 inhibitor maintenance therapy (yes versus no) (all P < 0.05). There was a non-significant trend for tumours with a gBRCA2 PV having CRS3 versus WT (odds ratio [OR] = 2.13, 95% confidence intervals [CI] 0.95–4.91; P = 0.0647). By contrast, tumours with a gBRCA1 PV were significantly less likely to have CRS3 than WT (OR = 0.35, 95%CI 0.14–0.91; P = 0.0291). Conclusions Germline BRCA1/2 genotype was not clearly associated with superior omental CRS. Further research is required to understand how HGSOC biology defines CRS.