Successful treatment of metastatic refractory gestational choriocarcinoma with pembrolizumab: A case for immune checkpoint salvage therapy in trophoblastic tumors

Abstract

Highlights Cure rates are high for choriocarcinoma, however chemoresistant disease often leads to death. High expression of PD-L1 suggests a role for checkpoint inhibitors in choriocarcinoma. Pembrolizumab should be considered for salvage therapy for chemoresistant choriocarcinoma.

An extrauterine extensively metastatic epithelioid trophoblastic tumor responsive to pembrolizumab

“…Recently there has been a strong interest in using immunotherapy in patients with trophoblastic disease since a significant portion of trophoblastic cells express PD-L1 receptors ( Veras et al, 2017 ). There have been reports of pembrolizumab successfully treating various forms of gestational trophoblastic diseases, including choriocarcinoma ( Clair et al, 2020 , Goldfarb et al, 2020 ). Additionally, there is a phase 2 clinical trial currently recruiting patients with chemo-resistant gestational trophoblastic disease for pembrolizumab treatment ( https://clinicaltrials.gov/ct2/show/NCT04303884 ).…”

Long-term survival in multiresistant metastatic choriocarcinoma after pembrolizumab treatment: A case report

“…In line, activity of pembrolizumab in chemotherapy-resistant GTN has been investigated in small cohorts and reported to be very successful in this patient group ( Huang et al, 2017 , Ghorani et al, 2017 , Choi et al, 2019 , Goldfarb et al, 2020 , Clair et al, 2020 ). However, only five cases of pembrolizumab treatment for chemotherapy-resistant choriocarcinoma have been reported to date.…”

“…Despite frustrating response to cytotoxic chemotherapy, she experienced full remission after pembrolizumab and has durable response of currently more than two years after end of treatment. Except for Clair et al ( Clair et al, 2020 ) no one has yet reported such a long progression-free follow-up. Even though reported observations appear promising for patients with metastasized chemotherapy resistant GTN, sizeable prospective multicenter trials will be necessary to substantiate current evidence on CPI treatment in this particular setting.…”

“…As the recent introduction of checkpoint inhibitor (CPI) therapy targeting programmed cell death ligand 1 (PD-L1) provided a new therapeutic strategy for several advanced solid tumors ( Herbst et al, 2016 ), the anti-PD-inhibitor pembrolizumab appears to be a promising therapeutic option for the subset of patients with choriocarcinoma experiencing chemotherapy resistance ( Huang et al, 2017 , Ghorani et al, 2017 , Goldfarb et al, 2020 , Clair et al, 2020 ).…”

Treatment of metastatic placental site trophoblastic tumor with surgery, chemotherapy, immunotherapy and coil embolization of multiple pulmonary arteriovenous fistulate

“…GTN (invasive mole and choriocarcinoma) strongly expresses PD-L1 ( Veras et al, 2017 ) and therefore the successful use of checkpoint inhibitors has increased. Pembrolizumab (anti-PD-1) has induced complete responses in 75–80% of unresectable, chemo-resistant GTN including cases that had failed high dose chemotherarpy ( Ghorani et al, 2017 , Clair et al, 2020 , Huang et al, 2017 ). Currently, it is unclear how to select responding cases as all are PD-L1 positive and mutational burden may be absent or extremely low in GTN.…”