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Abstract
Introduction/Background Several maintenance options are currently available for advanced ovarian carcinoma (AOC): mono-PARPi or bevacizumab alone or a combination olaparib/bevacizumab.
The appropriate strategy may be challenging and depends on clinical and molecular features.
We aimed at developing a score to measure how much AOC patients undergoing Neoadjuvant Chemotherapy (NACT) may really benefit from mono-PARPi maintenance therapy.
Methodology Retrospective data were collected from AOC patients receiving NACT, Interval Debulking Surgery (IDS) and subsequent mono-PARPi maintenance. Progression-free Survival (PFS) univariate and multivariate Cox regression analyses were carried out, identifying key significant parameters (p<0.05). A numerical value (based on the beta coefficient and on its ratio with absolute minimum beta value) was assigned to each parameters’ subcategory and all values were sum up at patient level. The variables included homologous recombination deficiency (HRD)/BRCA status, chemotherapy response score (CRS) at IDS, FIGO stage, residual tumor, favorable/unfavorable Kelim-score, and radiological response after NACT.
Results 164 patients were included in the analysis: 26(15.9%) CRS1, 78(47.6%) CRS2, 60(36.6%) CRS3; 44(26.8%) HRDtest negative; 31(18.9%) HRDtest positive BRCAwt, 89(54.3%) BRCA mutated (BRCAmut).
HRD/BRCA mutation status and CRS resulted the only two independent PFS prognostic factors (Figure1) and a score was assigned as follows: CRS1=0, CRS2=1 and CRS3=2; BRCAwt-HRDneg=0, BRCAwt-HRDpos=1 and BRCAmut=2. Patients were categorized according to the final score (0–4). The PFS was significantly worse in patients with a total score ≤1 (median PFS: 15.0, 95% CI: 11.4–18.6), intermediate for a score=2 (median PFS: 30.0 months, 95% CI: 24.3–35.7) and remarkably longer for patients with a score≥3 (median PFS not reached, 95% CI: 40.9%-67.5%) (figure 1).
Conclusion CRS and HRD/BRCA status are both independent prognostic factors of PFS in patients treated with mono-PARPi. This score may help in maintenance treatment’s tailoring for patients undergoing NACT+IDS. A confirmatory study including other maintenance options and a focus on patients with a score of 2 is already ongoing.
Disclosures C.M. reports Honoraria/consultation fees from AstraZeneca, MSD, GSK, Pharmamar and Menarini. R.E. reports Honoraria/consultation fees from GSK. U.M. UM has received personal fees (as consultant and/or speaker bureau) from Boehringer Ingelheim, Roche, MSD, Amgen, Thermo Fisher Scientific, Eli Lilly, Diaceutics, GSK, Merck and AstraZeneca, Janssen, Diatech, Novartis and Hedera unrelated to the current work. B.Y reports Honoraria/consultation fees from MSD, Astra-Zeneca, GSK- TESARO, BAYER, Roche-Genentech, ECS Progastrine, Novartis, LEK, Amgen, Clovis Oncology, Merck Serono, BMS, SEAGEN, Myriad, Menarini, Gilead, EISAI, Gilead. F.P. has received personal fees from menarini stem line unrelated to the current work. C.M.S. reports Honoraria/consultation fees from GSK. G.S. reports Honoraria/consultation fees from Covidien AG, AstraZeneca/MSD Olympus Europa, Baxter Healthcare GlaxoSmithKline, Intuitive Surgical Inc. A.F. reports Honoraria/consultation fees from AstraZeneca, MSD, Johnson&Johnson and Menarini. G.Z. reports Honoraria/consultation fees from GSK.