Immunotherapy in the treatment of chemoresistant gestational trophoblastic neoplasia - systematic review with a presentation of the first 4 Brazilian cases

Authors

  • Antonio Braga Young Leadership Physicians Program, Academia Nacional de Medicina, RJ, Rio de Janeiro, Brazil https://orcid.org/0000-0002-2942-6182
  • Elaine Balthar Postgraduate Program in Medical Sciences, Universidade Federal Fluminense, RJ, Niterói, Brazil https://orcid.org/0000-0002-9928-4968
  • Laís Cristhine Santos Souza Departament of Obstetrics, Escola Paulista de Medicina, Universidade Federal de São Paulo, SP, São Paulo, Brazil https://orcid.org/0000-0002-7786-6713
  • Michelle Samora Departament of Obstetrics, Escola Paulista de Medicina, Universidade Federal de São Paulo, SP, São Paulo, Brazil https://orcid.org/0000-0003-3387-513X
  • Matheus Rech Caxias do Sul Trophoblastic Disease Center, Faculdade de Medicina, Universidade de Caxias do Sul (UCS), RS, Caxias do Sul, Brazil https://orcid.org/0000-0002-2961-9443
  • José Mauro Madi Caxias do Sul Trophoblastic Disease Center, Faculdade de Medicina, Universidade de Caxias do Sul (UCS), RS, Caxias do Sul, Brazil
  • Joffre Amim Junior Postgraduate Program in Perinatal Health, Faculdade de Medicina, Maternidade Escola da, Universidade Federal do Rio de Janeiro, RJ, Rio de Janeiro, Brazil
  • Jorge Rezende Filho Postgraduate Program in Perinatal Health, Faculdade de Medicina, Maternidade Escola da, Universidade Federal do Rio de Janeiro, RJ, Rio de Janeiro, Brazil
  • Kevin M. Elias New England Trophoblastic Disease Center, Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Dana Farber Cancer Institute, Harvard Medical School, Boston, USA https://orcid.org/0000-0003-1502-5553
  • Neil S. Horowitz New England Trophoblastic Disease Center, Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Dana Farber Cancer Institute, Harvard Medical School, Boston, USA https://orcid.org/0000-0002-4854-0642
  • Sue Yazaki Sun Escola Paulista de Medicina, Universidade Federal de São Paulo, SP, São Paulo, Brazi
  • Ross S. Berkowitz New England Trophoblastic Disease Center, Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Dana Farber Cancer Institute, Harvard Medical School, Boston, USA https://orcid.org/0000-0002-7569-898X

DOI:

https://doi.org/10.1016/

Keywords:

Gestational trophoblastic neoplasia, Immunotherapy, PD-1/PD-L1 inhibitors, Pembrolizumab, Avelumab

Abstract

Objective: To evaluate the efficacy of immunotherapy for GTN treatment after methotrexate-resistance or in cases of multiresistant disease, through a systematic review, as well as to present the first 4 Brazilian cases of immunotherapy for GTN treatment.Methods: Three independent researchers searched five electronic databases (EMBASE, LILACS, Medline, CENTRAL and Web of Science), for relevant articles up to February/2023 (PROSPERO CRD42023401453). The quality assessment was performed using the Newcastle Ottawa scale for case series and case reports. The primary outcome of this study was the occurrence of complete remission. The presentation of the case reports was approved by the Institutional Review Board. Results: Of the 4 cases presented, the first was a low-risk GTN with methotrexate resistance unsuccessfully treated with avelumab, which achieved remission with sequential multiagent chemotherapy. The remaining 3 cases were high-risk multiagent-resistant GTN that were successfully treated with pembrolizumab, among which there were two subsequent gestations, one of them with normal pregnancy and healthy conceptus. Regarding the systematic review, 12 studies were included, only one of them on avelumab, showing a 46.7% complete remission rate. The remaining 11 studies were on pembrolizumab, showing an 86.7% complete remission rate, regardless of tumor histology. Both immunotherapies showed good tolerability, with two healthy pregnancies being recorded: one after avelumb and another after pembrolizumab. Conclusion: Immunotherapy showed effectiveness for GTN treatment and may be especially useful in cases of high-risk disease, where pembrolizumab achieves a high therapeutic response, regardless of the histological type, and despite prior chemoresistance to multiple lines of treatment.

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Published

2023-09-13

Issue

Vol. 78 (2023)

Section

Original Articles

How to Cite

Braga, A., Balthar, E. ., Souza, L. C. S. ., Samora, M. ., Rech, M. ., Madi, J. M. ., Amim Junior, J. ., Rezende Filho, J. ., Elias, K. M. ., Horowitz, N. S. ., Sun, S. Y. ., & Berkowitz, R. S. . (2023). Immunotherapy in the treatment of chemoresistant gestational trophoblastic neoplasia - systematic review with a presentation of the first 4 Brazilian cases. Clinics, 78, 100260 . https://doi.org/10.1016/