niraparib and Endometrial-Neoplasms

New molecular therapeutic approaches have emerged in recent years for advanced gynaecological cancers, including targeted therapies such as poly-ADP-ribose polymerase inhibitors (PARPi). These have demonstrated efficacy in high-grade serous ovarian cancers in patients carrying a mutation in the BRCA gene, which predisposes them to breast and ovarian cancers. Clinical and pre-clinical data suggest that the activity of PARPi inhibitors may not be limited to BRCA mutated tumours and may involve the homologous recombination pathway. These data raise the question of the potential efficacy of PARPi in advanced endometrial and cervical cancers where treatment options are currently limited. At present, there are few data available on the activity of PARPi in endometrial and cervical cancers, but some results seem promising. In this review, we present a synthesis of the available studies concerning PARPi in endometrial and cervical cancer.

Topics: Antineoplastic Agents; Cell Line, Tumor; Cisplatin; Clinical Trials as Topic; DNA Damage; DNA Repair-Deficiency Disorders; Endometrial Neoplasms; Female; Humans; Indazoles; Indoles; Ovarian Neoplasms; Papillomavirus Infections; Phthalazines; Piperazines; Piperidines; Poly(ADP-ribose) Polymerase Inhibitors; Uterine Cervical Neoplasms

This multi-centre, non-randomized, open-label, phase II trial (NCT03016338), assessed niraparib monotherapy (cohort 1, C1), or niraparib and dostarlimab (cohort 2, C2) in patients with recurrent serous or endometrioid endometrial carcinoma. The primary endpoint was clinical benefit rate (CBR), with ≥5/22 overall considered of interest. Secondary outcomes were safety, objective response rate (ORR), duration of response, progression free survival and overall survival. Translational research was an exploratory outcome. Potential biomarkers were evaluated in archival tissue by immunohistochemistry and next generation sequencing panel. In C1, 25 patients were enrolled, and CBR was 20% (95% CI: 9-39) with median clinical benefit duration of 5.3 months. The ORR was 4% (95% CI: 0-20). In C2, 22 patients were enrolled, and the CBR was 31.8% (95% CI: 16-53) with median clinical benefit duration of 6.8 months. The ORR was 14% (95% CI: 3-35). No new safety signals were detected. No significant association was detected between clinical benefit and IHC markers (PTEN, p53, MMR, PD-L1), or molecular profiling (PTEN, TP53, homologous recombination repair genes). In conclusion, niraparib monotherapy did not meet the efficacy threshold. Niraparib in combination with dostarlimab showed modest activity.

Topics: Biomarkers; Endometrial Neoplasms; Female; Humans; Neoplasm Recurrence, Local

Endometrial cancer (EC) is the second most common gynecologic malignancy in China, and the incidence and mortality rates have increased in recent years. Brain metastasis from EC is extremely rare, affecting only 0.3-1.16% of EC patients. The prognosis for patients with brain metastasis from EC is poor, with a median survival time of 3.5-6.5 months from the diagnosis of brain metastasis. Niraparib is a poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor that uses the concept of synthetic lethality in the presence of a mutation in the breast cancer susceptibility gene (BRCA). Niraparib is recommended as a maintenance treatment for ovarian cancer patients with platinum-sensitive relapse and has been shown to increase progression-free survival. Niraparib was found to enter the brain via the blood-brain barrier, which resulted in a higher concentration of the drug in the brain tissues and better tumor-suppressing effects. There was none report about the applications of PARP inhibitor for endometrial cancer with brain metastases. Here, we present the case of a 62-year-old woman whose Peripheral blood gene detection had shown BRCA1 mutation with brain metastases from high-grade serous carcinoma of the endometrium who was successfully treated with Niraparib and remained free of disease progression for 6 months.

Topics: Brain Neoplasms; China; Endometrial Neoplasms; Female; Humans; Indazoles; Middle Aged; Piperidines