Onkologie. 2024:18(5):305-310 | DOI: 10.36290/xon.2024.063

Current status of PARP inhibition in advanced, metastatic and recurent endometrial cancer

Monika Náležinská^{1, 2}, Josef Chovanec^{1, 2}

¹ Oddělení gynekologické onkologie Kliniky operační onkologie Masarykova onkologického ústavu, Brno

² Oddělení gynekologické onkologie Kliniky operační onkologie, Lékařská fakulta Masarykovy univerzity, Brno

Knowledge of molecular subtypes of endometrial cancer (EC) has led to major changes in the classification system, prognostic groups and, as a result, in therapeutic procedures in patients with advanced, metastatic and recurrent endometrial cancer (EC) in the last few years. The most significant shift in the difficult-to-treat cohort of patients with advanced, metastatic and recurrent EC since conventional chemotherapy is clearly the combination of the checkpoint inhibitor pembrolizumab with the antiangiogenic agent lenvatinib, independent of the presence of microsatellite instability (MSI) of tumor cells. In the MSI-high group of carcinomas, the administration of dostarlimab monotherapy appears to be very successful. iPARPs have been investigated in many therapeutic designs and it is evident that their therapeutic use will be in EC patients with homologous recombination deficiency, regardless of BRCA status. The mechanism of action of iPARP in EC patients is based on the frequent presence of PTEN mutation and TP53 mutation, which is related to the deficit in homologous recombination. iPARPs have both their own cytotoxic effect and sensitize EC cells to the effects of checkpoint inhibitors. The article summarizes the current evidence on preclinical research and clinical use of iPARP in patients with advanced, metastatic and recurrent EC. In the Czech Republic, olaparib is newly approved for administration in maintenance therapy in combination with durvalumab in patients with primarily advanced or recurrent EC (mismatch repair proficient - pMMR) who have not progressed on first-line systemic therapy in combination with paclitaxel, carboplatin and durvalumab.

Keywords: gynaecologic oncology, endometrial carcinoma, PARP inhibitors, PTEN mutation, P53 mutation, homologous recombination deficiency, immune checkpoint inhibitors.

Accepted: November 18, 2024; Published: November 28, 2024  Show citation