Immunotherapy Offers Hope in Another Rare Cancer Type

Immunotherapy in the Treatment of Gestational Trophoblastic Cancers

Some Terms and Their Meanings:

• Gestational means pregnancy and describes the process of embryonic development in the uterus.
• The placentais a circulatory structure belonging to both fetus and mother, providing almost every resource the baby needs in the womb.
• The cells surrounding the embryo during pregnancy are called trophoblasts .

The group of malignant tumors developing from abnormal proliferation of this placental trophoblastic tissue is called gestational trophoblastic cancers (GTC).

Gestational trophoblastic cancers are among the very rare cancers, estimated to occur once in every 40 thousand births. These cancers usually benefit greatly from chemotherapies, but some patients may experience cancer recurrence or develop resistance to chemotherapy.

Gestational trophoblastic cancers inherently express high levels of Programmed Cell Death Ligand 1 (PD-L1). As is known, immunotherapies have demonstrated efficacy in many cancer types and entered clinical use. Based on the high PD-L1 positivity of gestational trophoblastic cancers, two different immunotherapy agents have been studied in this cancer type. Avelumab (Bavencio) and pembrolizumab (Keytruda) were tested in two studies, both showing that immune checkpoint inhibitors were effective in chemotherapy-resistant gestational trophoblastic cancers.

The pembrolizumab study enrolled 4 high-risk patients with chemotherapy-resistant disease. A complete response in 3 patients was achieved. All four patients had PD-L1 levels > 90%. In the 3 complete responders, tumor-infiltrating lymphocytes were also highly positive. In addition to demonstrating pembrolizumab’s effect in this cancer type, this study highlighted the importance of tumor-infiltrating lymphocytes in immunotherapy response.

Preliminary avelumab data were reported at the 2018 European Cancer Congress (ESMO). The study evaluated 11 patients with chemotherapy-resistant gestational trophoblastic cancer. Avelumab reduced hCG, an important biomarker for monitoring this cancer, to normal levels in 95% of patients. Treatment-related side effects occurred in 73%. Only 2% were considered serious. An underactive thyroid accounted for 80% of these side effects. All adverse effects were considered manageable and non-life-threatening. We eagerly await publication of the study results including response rates.

Both studies enrolled very few patients. However, this cancer type is rare, and chemotherapy-resistant patients within this group are even less common. Ultimately, immunotherapy appears likely to become a good treatment option to consider in rare chemotherapy-resistant gestational trophoblastic cancers. We will eagerly await future studies showing efficacy in patients in this group who have not received chemotherapy.