Pamiparib for germline BRCA mutation-associated recurrent advanced ovarian, fallopian tube or primary peritoneal cancer.

Epithelial ovarian cancers are gynecological malignancies with the poorest prognosis. Intensive research over the past few years has demonstrated ovarian cancer is a type of cancer in which new molecularly targeted drugs significantly affect patients' fate and prognosis. These drugs are poly [ADP-ribose] polymerase (PARP) inhibitors, which are used for maintenance treatment. These molecules continue to be intensively studied--their combination with other targeted therapies is carefully evaluated as more of them are discovered. Four PARP inhibitors have been approved by the U.S. Food and Drug Administration (FDA) so far. Olaparib, rucaparib and niraparib are approved for various indications in epithelial ovarian cancer, fallopian tube or primary peritoneal cancer, while the PARP inhibitors for the treatment of breast cancer are olaparib and talazoparib. Olaparib is also approved for the treatment of pancreatic cancer as well as prostate cancer, and rucaparib is also approved for prostate cancer. Pamiparib (Partruvix) is a new, selective inhibitor of PARP-1 and PARP-2 which was discovered by BeiGene Ltd. On April 30, 2021, pamiparib obtained its first registration worldwide--it was approved in China for the treatment of women with recurrent ovarian, fallopian tube or primary peritoneal cancer with confirmed germline BRCA mutation.

The pharmacokinetics of pamiparib in the presence of a strong CYP3A inhibitor (itraconazole) and strong CYP3A inducer (rifampin) in patients with solid tumors: an open-label, parallel-group phase 1 study.

PURPOSE: Pamiparib is an investigational, selective, oral poly(ADP-ribose) polymerase 1/2 (PARP1/2) inhibitor that has demonstrated PARP-DNA complex trapping and CNS penetration in preclinical models, as well as preliminary anti-tumor activity in early-phase clinical studies. We investigated whether the single-dose pharmacokinetic (PK) profile of pamiparib is altered by coadministration of a strong CYP3A inducer (rifampin) or a strong CYP3A inhibitor (itraconazole) in patients with solid tumors. METHODS: In this open-label, phase 1 study, adults with advanced solid tumors received either oral pamiparib 60 mg (days 1 and 10) and once-daily oral rifampin 600 mg (days 3-11) or oral pamiparib 20 mg (days 1 and 7) and once-daily oral itraconazole 200 mg (days 3-8). Primary endpoints included pamiparib maximum observed concentration (Cmax), and area under the plasma concentration-time curve from zero to last quantifiable concentration (AUC0-tlast) and infinity (AUC0-inf). Secondary endpoints included safety and tolerability. RESULTS: Rifampin coadministration did not affect pamiparib Cmax (geometric least-squares [GLS] mean ratio 0.94; 90% confidence interval 0.83-1.06), but reduced its AUC0-tlast (0.62 [0.54-0.70]) and AUC0-inf (0.57 [0.48-0.69]). Itraconazole coadministration did not affect pamiparib Cmax (1.05 [0.95-1.15]), AUC0-tlast (0.99 [0.91-1.09]), or AUC0-inf (0.99 [0.90-1.09]). There were no serious treatment-related adverse events. CONCLUSIONS: Pamiparib plasma exposure was reduced 38-43% with rifampin coadministration but was unaffected by itraconazole coadministration. Pamiparib dose modifications are not considered necessary when coadministered with CYP3A inhibitors. Clinical safety and efficacy data will be used with these results to recommend dose modifications when pamiparib is coadministered with CYP3A inducers.

Gynaecological cancers coexisting with pregnancy - a literature review.

The coexistence of malignant tumour and pregnancy is a state of simultaneous occurrence of two completely contradictory philosophical and biological phenomena - the development of a new life and a life-threatening terminal illness. Finally, a physician - in fact the whole team of doctors - is facing the fight for two lives: of the mother and her unborn child. The incidence of malignant disease in pregnancy is 0.05 to 0.1%. This condition is a major challenge for physicians because there are no randomised studies that could be the basis to choose the therapeutic methods - the medical knowledge merely comes from case reports, registries, and observational studies. The following cancers most often coexist with pregnancy: gynaecological neoplasm (especially cervical and ovarian cancer), breast cancer, lymphatic system neoplasm, and melanoma. Formerly, the diagnosis was clearly the necessity of abortion. Today - although unskilled doctors still propose the only therapeutic option - termination of pregnancy is not the only solution. The past few years have seen the updating of reports and guidelines for the management of pregnant women with cancer. This paper is a review and summary of the information from these publications.