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

Gynecol Oncol. 2023 Jun:173:98-105. doi: 10.1016/j.ygyno.2023.04.002. Epub 2023 Apr 25.

Abstract

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.

Keywords: High-grade epithelial ovarian cancer; Local therapy; Oligometastatic progression; PARP inhibitors.

Publication types

  • Multicenter Study

MeSH terms

  • Carcinoma, Ovarian Epithelial / drug therapy
  • Female
  • Humans
  • Neoplasm Recurrence, Local / drug therapy
  • Ovarian Neoplasms* / drug therapy
  • Poly(ADP-ribose) Polymerase Inhibitors*
  • Retrospective Studies

Substances

  • Poly(ADP-ribose) Polymerase Inhibitors