Current Evidence on Immunotherapy for Gestational Trophoblastic Neoplasia (GTN)

Abstract

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.

Choriocarcinoma masquerading as lumbar spinal tumor: Case report and literature review

“…Despite these successful cases proving the effectiveness of pembrolizumab in GTN, till nowadays no reviews have been provided the data to identify the safety of pembrolizumab in this disease setting so that pembrolizumab is not licensed for application in GTN for the moment. [17] On the other hand, finally the patient died from pulmonary embolism. Patients with cancer are high-risk groups for venous thromboembolism (VTE).…”

“…Despite these successful cases proving the effectiveness of pembrolizumab in GTN, till nowadays no reviews have been provided the data to identify the safety of pembrolizumab in this disease setting so that pembrolizumab is not licensed for application in GTN for the moment. [ 17 ]…”

Case report: Multidrug resistant gestational trophoblastic neoplasia: focus on failure of immunotherapy and success of high-dose chemotherapy

“…Over the last decade, immunotherapy has already proved its effectiveness in the treatment of melanoma, lung cancer and kidney cancer, and is revolutionizing the treatment of many other cancers ( 12 , 13 ). GTNs have a particular genomic profile with a high paternal predominance capable of activating an immune response, making them an ideal target for immunotherapy ( 14 , 15 ). This new therapeutic approach is based on the fact that the programmed death ligand 1 (PDL-1) binding protein is highly expressed in normal placentas and in all GTD subtypes ( 16 – 23 ).…”

The fertility-sparing treatment and outcome of epithelioid trophoblastic tumor isolated to lung: a case report and review literature

“…Regarding adverse actions on the reproductive system of platinum-based chemotherapy, there are no reported cases utilizing the GnRH agonist protocol for ovarian protection before treatment so far. In recent years, immunotherapy, like pembrolizumab (anti-PD-1), has been introduced into GTN, especially unresectable, chemotherapy-resistant GTN cases ( 25 ). ETT also indicates high PD-1/PD-L1 gene expression ( 26 , 27 ).…”