Epithelial Ovarian Cancer (EOC) is the second most deadly gynecologic cancer and the third most common cancer worldwide [1,2]. First-line treatment for EOC is well standardized with a primary debulking surgery (PDS) followed by platinum-based chemotherapy (PBCT). If PDS is not possible, neoadjuvant chemotherapy followed by interval debulking surgery (IDS) is recommended [3]. Maintenance therapy with anti-VEGF and/or PARP inhibitors (PARPi) is then proposed, depending on molecular, patient, and disease characteristics [3]. Although most patients achieve a partial or complete response, 80 % will relapse [4,5]. Relapse treatment has been less well codified and, until recently, was primarily based on the Platinum Free Interval (PFI) [3]. The PFI is defined as the interval between the last cycle of PBCT and the next progression or relapse. Several studies have shown that PFI is a key prognostic and predictive factor and that the longer the PFI, the more likely patients are to respond to second line PBCT with an improvement in overall survival [[6], [7], [8]]. Until recently, oncologists have based their treatment decisions upon relapse on PFI, using a 6-month cut-off for rechallenge with PBCT, even in the absence of reliable data on the choice of threshold, as highlighted by the Sixth Ovarian Cancer Consensus Conference (OCCC) of the Gynecologic Cancer InterGroup [2]. Clinical trials also rely on PFI to categorize patients as platinum sensitive or resistant and use it as an inclusion criterion. Thus, PFI is part of the drug approval process [9].

However, this definition has been questioned, especially by the Fifth and Sixth OCCC and by the recent ESMO/ESGO guidelines because of its numerous limitations [3,10]. First, the definition of PFI is not consensual as it can be defined in different ways depending on the frequency and the type of follow-up examinations (clinical exam, CT scan, MRI, PET…), for which there are no precise recommendations [6,9]. It has been retrospectively described that even patients with a PFI of less than 6 months are likely to respond to PBCT, especially BRCA mutated or homologous recombination deficiency (HRD) patients who are naïve to PARPi therapy [11]. Even patients older than 65 years with a PFI between 3 and 6 months have a reduced risk of death with a PBCT compared to non‑platinum monotherapy [12]. A PFI of more than 6 months does not guarantee a response to chemotherapy, but is associated with higher response rates [13]. Platinum resistance is better defined as a continuous variable [10,14]. The OCCC recommends discussing PBCT at relapse regardless of the PFI, considering localization, symptoms, histology, residual toxicity, and patient preference. Cancer biology must be taken into account as it alters treatment response, particularly according to BRCA and HRD status [9,10]. Furthermore, studies validating the use of PFI date back to the 1990s when platinum chemotherapy was the only treatment available. With the advent of targeted therapies, this definition seems outdated.

Real-world data is essential to assess the accuracy of PFI and to evaluate the impact of targeted therapies on subsequent treatments. The French National Epidemiological Strategy and Medical Economics (ESME) is a multicentric cohort that aims to centralize information on patients treated in one of the French Comprehensive Cancer Centers. The aim of this observational study was to evaluate the impact of PFI on progression-free survival (PFS) and overall survival (OS) of subsequent lines in patients with recurrent epithelial ovarian cancer, using the ESME database. An exploratory analysis was conducted to evaluate the influence of prior-line treatment on the response to subsequent chemotherapy. To validate these findings, we also performed a secondary analysis within the more homogeneous subgroup of high-grade serous carcinomas (HGSC).