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Abstract
Introduction/Background PARP inhibitors (PARPi) maintenance after Platinum (Pt) based chemotherapy (CT) significantly improves progression-free survival (PARPi-PFS) and PFS after subsequent (ssq) CT (PARPi-PFS2) in relapsed high grade serous ovarian cancer (HGSOC). Data regarding ssq CT is scarce, and PARPi/Pt crossed mechanisms of resistance may impact on outcome of ssq Pt. We provide Real-world-data on this issue.
Methodology We included HGSOC p treated with ssq CT after progression to maintenance PARPi until 15th Jul 2020 in 3hospitals. Endpoints were related to this ssq CT: objective response rate (ORR), median(m) progression-free survival (PFS) and overall survival (OS). Multivariate Cox and logistic regression models were adjusted by BRCA status and Pt-free interval (PFI) (6–12 months(mo) vs ≥12 mo). Adjusted hazard ratios (aHR) and odds ratios (aOR) of the risk of progression/death and ORR, respectively, were reported with 95% confidence intervals (CI).
Results 56p were identified (32p BRCAmut; 1p BRIP1mut). 4p (7.1%) received PARPi after 1st line CT, 26 (46.4%) after 2nd line and 26 (46.4%) after ≥3rd line. 34p (60.7%) received olaparib and 22 (39.3%) niraparib. m-PARPi-PFS in the recurrent setting was 7.5 mo (longer in BRCAmut: 10.1 vs 5.5 mo, p 0.03). m-PARPi-PFS2 was 15.8 mo (longer in BRCAmut: 20.9 vs 15.4 mo, p 0.07).
Endpoints regarding ssq CT are shown in table1. ORR to ssq Pt was 33.3% and progression disease without any response 28.6%. ORR in p who received ssq Pt-free CT, ssq Pt with PFI 6–12 mo, and ssq Pt with PFI≥12 mo were 33.3%, 23.8% and 42.8%, respectively. Five complete responses occurred among BRCAmut p that had received PARPi in the recurrent setting. mPFS and mOS were significantly longer in the PFI≥12 subgroup vs the others (figure1).
Focusing in p receiving ssq Pt, when adjusting by BRCA status: aOR of ORR in p with PFI≥12 vs 6–12 mo was 0.56 (95% CI: 0.13 – 2.30), aHR of mPFS between these two subgroups was 0.61 (95% CI: 0.30–1.20; p 0.16), and aHR of mOS was 0.20 (95% CI: 0.7–0.61, p 0.005). Results did not change when excluding the 4p who received PARPi as 1st line.
Ssq CT-OS (left) and ssq CT-PFS (right)
Endpoints regarding ssq CT
Conclusion A trend towards higher benefit from ssq Pt after PARPi was observed in the PFI≥12 subgroup. Benefit from ssq Pt after PARPi in the PFI 6–12 subgroup was similar to benefit from CT in the non-Pt subgroup. The role of ssq Pt after PARPi in the PFI 6–12 subgroup warrants further research.
Disclosures Andrea Plaja: travel grant for attending scientific meeting (Roche, Angelini).
Marta Gil-Marin: speaking (Roche, Astra Zeneca, Pharmamar) and travel grants (Roche, Pharmamar, MSD).
Beatriz Pardo: speaking (Roche, Astra Zeneca, MSD) and travel grants (Roche, MSD, GSK).
Josep Maria Piulats: advisory board (Astra Zeneca, MSD, Clovis, BeiGene) and travel grants (Astra Zeneca, MSD, BeiGene).
María Pilar Barretina: advisory board (Roche, Astra Zeneca, GSK, Clovis Oncology), speaking (Roche, Astra Zeneca, GSK, Clovis Oncology, Pharmamar) and travel grants (Roche, GSK, Astra Zenaca, Pharmamar).
Clàudia Fina: travel grants (Roche, MSD, Pfizer, Bristol-Myers)
Margarita Romeo: advisory boards (AZ, TESARO) and travel grants (Pfizer).
Iris Teruel, Anna Esteve and Andrea Gonzalez have nothing to disclosure.