Introduction/Background In PAOLA-1/ENGOT-ov25 (NCT02477644), maintenance PARP inhibitor (PARPi) olaparib+bevacizumab improved progression-free survival (PFS) in patients with homologous recombination-deficient (HRD+) advanced ovarian cancer (Ray-Coquard. NEJM 2019;381:2416–28). Post-hoc analysis showed the efficacy of subsequent chemotherapy at relapse was reduced in patients who progressed during versus after olaparib treatment (Harter. Presented at ASCO 2023).

In the OReO/ENGOT-ov38 trial (NCT03106987), olaparib rechallenge conferred a modest but statistically significant PFS benefit in patients with platinum-sensitive ovarian cancer (Pujade-Lauraine. Ann Oncol 2021;32:S1308–9), the majority of whom had received initial PARPi therapy in the relapsed setting and, therefore, were most likely to have progressed under PARPi maintenance. We explored PARPi rechallenge in patients who received platinum-based combination therapy (PBC) followed by PARPi (PBC>PARPi) as first subsequent therapy (FST) after progression on first-line treatment in PAOLA-1.

Methodology To explore the efficacy of PBC>PARPi, median time from FST to second subsequent therapy (SST) was analysed post-hoc by timing of progression (during/after olaparib) and tumour HRD status.

Results 544 patients progressed and received subsequent chemotherapy. Time from FST to SST was longer in patients receiving PBC>PARPi (n=159) as FST than in patients receiving PBC without PARPi maintenance (n=293) and was shortest in patients who progressed during olaparib (table 1).

Myelodysplastic syndrome, acute myeloid leukaemia or aplastic anaemia occurred in 3/82 (3.7%) patients in the control arm and no patients who received olaparib. No unexpected toxicity was observed.

Conclusion In this post-hoc exploratory analysis of PAOLA-1, subsequent PBC>PARPi rechallenge led to better outcomes than PBC alone in patients who received olaparib+bevacizumab. Efficacy appeared to depend on whether progression occurred during or after olaparib treatment. Results build on observations from OReO that PARPi rechallenge could be considered for patients responding to PBC, but are limited by small patient numbers and loss of randomisation, and need to be confirmed in a larger randomised study.

Disclosures This work was supported by ARCAGY Research, AstraZeneca, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and F. Hoffmann-La Roche.