PARP inhibitors (PARPi) prolongation after local therapy for oligo-metastatic

PARP inhibitors (PARPi) prolongation after local therapy for oligo-metastatic progression in relapsed ovarian cancer patients

Thibault Gauduchon, Maria Kfoury, Domenica Lorusso, Anne Floquet, Jole Ventriglia, Hélène Salaun, Malak Moubarak, Romain Rivoirard, Laura Polastro, Laure Favier, Benoit You, Dominique Berton, Thibault de la Motte Rouge, Laura Mansi, Cyril Abdeddaim, Karine Prulhiere, Laurence Lancry Lecomte, Magali Provansal, Cécile Dalban, Isabelle Ray-Coquard

Multicenter Study  Gynecol Oncol. 2023 Jun. Epub 2023 Apr 25.

Background: PARP inhibitors (PARPi) have revolutionized the management of high-grade epithelial ovarian cancer (HGOC) treatment. However, a significant number of patients relapse or progress under PARPi, leading to the introduction of a new line of systemic therapy such as chemotherapy. In patients with a limited number of metastatic sites at progression, -referred to as an oligometastatic progression- a potential indication for local therapy followed by re-introduction or continuation of PARPi treatment rather than initiating a new line of chemotherapy could be proposed. However, the impact of such strategies on progression free survival (PFS) in these patients remains unknown.

Methods: This international multicenter retrospective study evaluated the efficacy of PARPi continuation or re-introduction in patients with HGOC after local treatment for oligometastatic progression. The main objective was to assess PFS under PARPi after local therapy (PFS post-LT). Secondary objectives included safety and overall survival (OS).

Results: 74 patients were identified in 20 centers between April 2020 and November 2021. 65% of patients were BRCA mutated and 92% had received ≥2 lines of prior systemic chemotherapy before the initial introduction of PARPi. Main progression sites were lymph nodes (42%), peritoneum (27%), liver (16%), other visceral (16%) and abdominal wall (4%). Local therapies included radiotherapy (45%), surgery (43%), both (7%), percutaneous thermal ablation (4%) or chemoembolization (1%). Median PFS post-LT was 11.5 months [95% CI 7.4; 17.2]. After a median follow up of 14.8 months, 6 patients (8.1%) discontinued PARPi due to toxicity. The 1-year overall survival rate was 90.7% [95% CI 79.1; 96.0].

Conclusions: With close to one year without progression or introduction of a new line of systemic therapy, this study reports the feasibility and potential benefit of this original strategy in patients with oligometastatic progression under PARPi.

PMID: 37105063
DOI: 10.1016/j.ygyno.2023.04.002

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