Article Text

Download PDFPDF

43 Hyperprogression of choriocarcinoma after treatment with pembrolizumab
  1. N Yeganeh Kazemi1,
  2. C Langstraat2 and
  3. J Weroha3
  1. 1Medical Scientist Training Program, Mayo Clinic Alix School of Medicine, USA
  2. 2Department of Obstetrics and Gynecology, USA
  3. 3Department of Medical Oncology, USA


Objectives We describe the case of a woman with non-gestational, extra-gonadal, choriocarcinoma who developed hyperprogression on pembrolizumab and review the literature regarding this phenomenon in gynecologic cancers.

Methods The medical record was reviewed with close attention to β-hCG trends associated with multiple lines of therapy. A literature review was done to summarize the potential mechanisms behind hyperprogression in response to immune checkpoint blockade.

Results A 49-year old, G2P2 woman with no history of molar pregnancy presented with high-grade fevers, persistent cough and right upper quadrant pain. β-hCG was elevated at 79,000 IU/L and a liver biopsy revealed choriocarcinoma but imaging did not identify a primary tumor. She was initially managed as gestational trophoblastic tumor (GTD) and achieved a brief complete radiographic and biomarker response with EMA-CO chemotherapy. Subsequently, she received TPE and later 5FU. Eventually, molecular analysis was consistent with non-gestational choriocarcinoma and IHC showed 22% PD-L1 positivity (tumor proportion score). She received pembrolizumab but β-hCG levels rose abruptly and uncharacteristically through all three cycles. The patient developed dyspnea on exertion, cough, and right flank pain. CT imaging demonstrated marked progression of liver metastases and innumerable new pulmonary metastases. She died 10 weeks after starting pembrolizumab.

Conclusions Non-gestational choriocarcinoma is an exceedingly rare and aggressive primary germ cell tumor. Treatment depends on proper diagnosis and management. Few cases of hyperprogression have been described in gynecologic cancers treated with immune checkpoint inhibitors. Mutations in pathways affecting immune-activation and p53 regulation may account for hyperprogression after pembrolizumab in this patient.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.