Introduction The benefit of poly (ADP-ribose) polymerase inhibitor (PARPi) retreatment after PARPi resistance, as well as the optimal regimen and timing, remains ambiguous.

Methods All patients included in this study were pathologically diagnosed with epithelial ovarian cancer and established disease progression with RECIST1.1 criteria during the initial PARPi treatment. Following several lines of therapies, the patients were re-treated with PARPi monotherapy or PARPi combined with antiangiogenic agents. The primary outcome to assess the benefit of PARPi re-treatment was progression-free survival (PFS), defined as the time from re-treatment of PARPi to the first subsequent therapy or death. Proteomic analysis was conducted in 7 patients receiving initial PARPi treatment and 4 patients receiving PARPi retreatment combined with anti-angiogenic agents.

Results A total of 90 patients were enrolled in the study. 56 (62.2%) patients received PARPi monotherapy re-treatment, and 34 (37.8%) patients received PARPi re-treatment combined with anti-angiogenic agents. Patients re-treated with PARPi still had certain survival benefit, with a median PFS of 4.0 months, and combination with anti-angiogenic agents would have a better survival benefit (median PFS: 5.9 vs. 3.3 months, p<0.0001). Multivariate analysis revealed that the regimens of PARPi re-treatment (combination with anti-angiogenic agents vs. monotherapy, HR=0.304, p=0.000) and treatment phase of PARPi re-treatment (maintenance vs. salvage, HR=0.390, p=0.001) were association with the benefit of PARPi re-treatment. Proteomics analysis indicated that anti-angiogenic agents played a major role in the combination regimen of PARPi re-treatment.

Conclusion/Implications For PARPi-resistant patients, maintenance therapy for PAPRi re-treatment combined with anti-angiogenic agents is recommended for superior survival benefit.