The role of immunotherapy in the management of metastatic/recurrent female reproductive system neoplasms

Abstract

In 2019 malignant neoplasms of the female reproductive system (ovarian cancer, (OC), endometrial carcinoma (EC) and cervical cancer (CC) were diagnosed in 58 860 patients – 17.6% of all malignant tumors in women in Russia. The morbidity and mortality rates from these neoplasms remain high over the past 10 years. This article provides a detailed review of the current evidence base for the use of various immunotherapeutic agents in mentioned malignant neoplasms. It has been demonstrated that in relapsed OC (ROC), the only proved indication for immunotherapy is tumors with microsatellite instability (MSI), whereas PD-L1 does not have an independent role in this disease. MSI occurs in approximately 8% of patients with metastatic OC. A significantly higher frequency MSI — up to 25% is detected in metastatic EC. MSI-positive subtype of the disease is characterized by an extremely high sensitivity to immunotherapy - the rate of objective response with pembrolizumab exceeds 50%. For MS-stable EC, the combination of pembrolizumab and lenvatinib is an effective therapeutic option. In advanced CC, on the other hand, PD-L1 has a predictive role for immunotherapy efficacy — the KEYNOTE-158 study showed that about 15% of patients with extensively pretreated metastatic PD-L1-positive CC can achieve long-term remission with pembrolizumab compared to 0% in PD-L1 negative tumors. Current evidence shows that PD-L1 expression can be observed in ≥ 30% of patients.

Keywords

• cervical cancer
• uterine cancer
• endometrial carcinoma
• ovarian cancer
• pembrolizumab
• lenvatinib
• targeted therapy
• immunotherapy
• msi
• pd-l1