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Meta-Analysis
. 2025 Mar 2:80:100583.
doi: 10.1016/j.clinsp.2025.100583. eCollection 2025.

Pembrolizumab in gestational trophoblastic neoplasia: Systematic review and meta-analysis with sub-group analysis of potential prognostic factors

Marcio Barcellos  1 , Antonio Braga  2 , Matheus Machado Rech  3 , Solange Artimos de Oliveira  4 , Jose Mauro Madi  3 , Sue Yazaki Sun  5 , Jorge de Rezende-Filho  6 , Kevin M Elias  7 , Neil S Horowitz  7 , Ross S Berkowitz  7
Affiliations
Meta-Analysis

Pembrolizumab in gestational trophoblastic neoplasia: Systematic review and meta-analysis with sub-group analysis of potential prognostic factors

Marcio Barcellos et al. Clinics (Sao Paulo). .

Abstract

Objective: To assess the performance of pembrolizumab for the treatment of Gestational Trophoblastic Neoplasia (GTN).

Methods: The Medical Subject Headings related to immunotherapy/pembrolizumab and GTN were used alone or in combination to retrieve relevant articles. The authors searched in EMBASE, MEDLINE/PubMed, Elsevier's Scopus, and Web of Science until November/2024. The authors included any randomized controlled trials, cohort studies, case series, and case reports focusing on pembrolizumab treatment in GTN. Meta-analysis of proportions was carried out employing a random-effects model. The meta-analysis employed the inverse variance method, with the arcsine link function for the analysis of proportional data. All analyses were performed using Stata 18. For all analyses, a p-value < 0.05 indicated statistical significance. This study was registered on PROSPERO (CRD42023493329).

Results: A total of 550 studies were identified after a literature search among which 15 original studies were included in the systematic review and in the meta-analysis. Pembrolizumab induced complete sustained remission in 71.59% (95% CI 53.27‒84.78%; I2 = 0.00%, H2 = 1.00, p = 0.90) of cases. The subgroups meta-analysis showed pembrolizumab had similar performance, regardless of age (< 40 vs. ≥ 40-years-old, p = 0.38), GTN histopathology (Placental Site Trophoblastic Tumor [PSTT], Epithelioid Trophoblastic Tumor [ETT]/noninvasive mole/others versus invasive mole/choriocarcinoma, p = 0.48), time from diagnosis to the beginning of immunotherapy (< 4 vs. ≥ 4-years, p = 0.84), pembrolizumab combined with chemotherapy (yes vs. no, p = 0.66).

Conclusions: Pembrolizumab seems an effective treatment for patients with high-risk GTN with chemoresistant or relapsed disease, including cases of PSTT/ETT, notwithstanding patient age, time to initiate immunotherapy and whether or not it was associated with chemotherapy.

Keywords: Choriocarcinoma; Gestational trophoblastic neoplasia; Immunotherapy; PD-1/PD-L1 inhibitors; Pembrolizumab.

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Conflict of interest statement

Conflicts of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig 1
Fig. 1
Prisma 2009 Flow Diagram.
Fig 2
Fig. 2
Forest plot and pooled proportion of patients with sustained remission after pembrolizumab for gestational trophoblastic neoplasia.
Fig 3
Fig. 3
Forest plot and pooled proportion of various subgroups of factors that may influence the efficacy of pembrolizumab treatment.
Fig 4
Fig. 4
Forest plot and pooled proportion of patients with sustained remission after pembrolizumab considering the leave-one-out sensitivity analysis.
Fig 5
Fig. 5
Forest plot and pooled proportion of patients with sustained remission after pembrolizumab considering only case series analysis.
See this image and copyright information in PMC

References

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