Current Evidence on Immunotherapy for Gestational Trophoblastic Neoplasia (GTN).

Abstract

Simple SummaryGestational trophoblastic neoplasia (GTN) is a rare tumor group that arises from the malignant transformation of placental tissue. Based on the evaluation of International Federation of Gynecology and Obstetrics (FIGO) anatomic staging and FIGO prognostic score, GTN is divided into low-, high-, and ultra-high-risk groups if the score obtained is less than or equal to 6, greater than 6 or greater than 12, respectively. The standard treatment is chemotherapy, using a single agent in low-risk disease and multiagent chemotherapy in high- and ultra-high-risk GTN. In chemoresistant forms of GTN, the use of immune checkpoint inhibitors, such as anti-PD-1 or anti-PD-L1/2, could represent a new therapeutic strategy. In this study, we evaluate the available evidence on immune checkpoint inhibitors for GTN treatment.Background: Gestational trophoblastic disease includes a rare group of benign and malignant tumors derived from abnormal trophoblastic proliferation. Malignant forms are called gestational trophoblastic neoplasia (GTN) and include invasive mole, choriocarcinoma, placental site trophoblastic tumor and epithelioid trophoblastic tumor. Standard treatment of GTN is chemotherapy. The regimen of choice mainly depends on the FIGO prognostic score. Low-risk and high-risk GTN is treated with single-agent or multiagent chemotherapy, respectively. In the case of chemoresistance, immunotherapy may represent a new therapeutic strategy. Methods: Literature obtained from searches on PubMed concerning GTN and immunotherapy was reviewed. Results: Programmed cell death 1 (PD-1) and its ligands (PD-L1/2) are expressed in GTN. Published data on PD-1/PD-L1 inhibitors alone in GTN were available for 51 patients. Pembrolizumab is an anti-PD-1 inhibitor used in chemoresistant forms of GTN. In the TROPHIMMUN trial, Avelumab, a monoclonal antibody inhibiting PD-L1, showed promising results only in patients with GTN resistant to monochemotherapy. Conversely, in patients with resistance to multiagent chemotherapy, treatment with Avelumab was discontinued due to severe toxicity and disease progression. The association of Camrelizumab and Apatinib could represent a different treatment for forms of GTN refractory to polychemotherapy or for relapses. Conclusions: Anti-PD-1 or anti-PD-L1 might represent an important new treatment strategy for the management of chemoresistant/refractory GTN.