The role of Chemotherapy Response Score (CRS) in the decision making process for advanced high grade serous ovarian cancer patients undergoing neoadjuvant chemotherapy.

person Claudia Marchetti Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy info_outline Claudia Marchetti, Raffaella Ergasti, Filippo Maria Capomacchia, Diana Giannarelli, Carolina Maria Sassu, Gian Franco Zannoni, Giovanni Scambia, Anna Fagotti

Authors person Claudia Marchetti Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy info_outline Claudia Marchetti, Raffaella Ergasti, Filippo Maria Capomacchia, Diana Giannarelli, Carolina Maria Sassu, Gian Franco Zannoni, Giovanni Scambia, Anna Fagotti Organizations Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy, Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Roma, Italy Abstract Disclosures Research Funding Institutional Funding Fondazione Policlinico Universitario Agostino Gemelli IRCCS Background: The role of chemotherapy response score (CRS) in predicting PARP inhibitors (PARPi) response for high grade serous Advanced Ovarian Cancer (AOC) patients undergoing Neoadjuvant Chemotherapy (NACT) has never been investigated. Also, the correlation between CRS and Homologous Recombination status (HRs) is unclear. Methods: In this observational retrospective study, we collected data from patients with high grade serous AOC, FIGO stage III-IV, undergoing NACT and subsequent Interval Debulking Surgery (IDS) from 2017 to 2021. KELIM score, CRS and BRCA status were considered; additionally, HRs (Foundation test) was reported when available. Primary endpoint was Progression Free Survival (PFS) according to CRS (CRS 1/2 vs 3) in patients receiving PARPi. Results: We enrolled 309 patients; 102 had CRS3 and 193 had CRS1/2 (14 were undetermined). Patients with CRS3 and PARPi maintenance showed the best prognosis, compared to all other subgroups (median PFS Not Reached, p =0.014); additionally, in the BRCA wild type population, CRS3 was predictive of longer survival (median PFS for the CRS3+PARPi BRCAwt population 24 months compared with 15 months for the CRS1/2+PARPi BRCAwt patients, p =0.041). Furthermore, among the 44 patients with known HRs, 59.1% of HR Deficiency (HRD) positive patients had CRS3, conversely 22.7% of HRD negative ones had a CRS3 ( p =0.048) Finally, we found out that a favorable KELIM was significantly associated with CRS3 in the all-comers patients ( p =0.007) and in the BRCAwt ( p =0.04), but it was not predictive of PARPi response. Conclusions: Our findings suggested that the higher the CRS at the interval cytoreduction, the better the subsequent PARPi response. CRS correlates with PARPi response, as the HRD test does in other clinical trials and it may be considered as a surrogate of HRD status. We have planned to retrospectively perform HR test on a total sample size of 77 patients who received PARPi to corroborate this hypothesis. Patients (N) Median PFS (months, CI 95%) p value All-Comers CRS 3 + PARPi 47 NR - CRS 1/2 + PARPi 106 26 0.014 CRS 3 - NO PARPi 23 18 <0.001 CRS 1/2- NO PARPi 61 13 <0.001 BRCA-wt population CRS 3 + PARPi 24 24 - CRS 1/2 + PARPi 53 15 0.041 CRS 3 - NO PARPi 19 18 0.161 CRS 1/2 + No PARPi 48 13 0.001