Étude visant à mieux comprendre quel est le meilleur moment pour réaliser la chirurgie dans le cancer de l’ovaire selon les caractéristiques génétiques de la tumeur

Objectif(s) de la recherche et intérêt pour la santé publique

Finalité de l'étude

Objectifs poursuivis

Domaines médicaux investigués

Bénéfices attendus

Recent evidence highlights the major prognostic impact of complete cytoreduction in advanced ovarian cancer, particularly in patients with homologous recombination deficiency (HRD), while suggesting that the optimal timing of surgery may vary according to the tumor’s genetic profile.
The objectives of this project are :
- To study the association between PFS and surgical timing according to HRD status
- To study the association between PFS/OS and surgical timing depending on the type of genetic anomaly (BRCAmut/wt, BRCA 1/ 2, HRD score) and surgical quality (complete/residual disease), and maintenance treatment
- To assess the effect of residual disease in prognostic outcome depending both on genetic anomalies and maintenance treatment administration
- To investigate the relationship between surgical timing, genetic anomalies (HRD/HRD-negative, BRCA mutations, BRCA wild type), and relapse patterns (peritoneal, lymph node, distant).

For that, about 806 patients with clinical and biological data will be analyzed from the PAOLA-1 clinical trial "Randomized, Double-Blind, Phase III Trial of Olaparib vs. Placebo in Patients with Advanced FIGO Stage IIIB – IV High Grade Serous or Endometrioid Ovarian, Fallopian Tube, or Peritoneal Cancer treated with standard First-Line Treatment, Combining Platinum-Taxane Chemotherapy and Bevacizumab Concurrent with Chemotherapy and in Maintenance".

PFS rates will be estimated using the Kaplan-Meier method and presented by groups (Surgical timing / HRD status). Comparison between groups will be performed using the Logrank test. Multivariable analysis will be performed using Cox proportional hazard model. Hazard ratios (HR) will be estimated with their 95%CI. Interaction between surgical timing and HRD status will be then evaluated.
To account for cofounding factors a propensity score matched analysis and IPTW adjustment will be performed to assess the impact of the timing of surgery according to HRD status on PFS. To avoid the guarantee-time bias, landmark analysis and Cox model with a time-dependent variable will be also considered.
A similar methodology to the primary objective will be used to study the association between PFS/OS and surgical timing according to the type of genetic anomaly, surgical quality and maintenance treatment administration.