# Strategies for managing EMA/CO resistant in gestational trophoblastic neoplasia a systematic review and meta analysis

## TL;DR

This study reviews and analyzes treatment options for gestational trophoblastic neoplasia that is resistant to standard chemotherapy, identifying effective salvage regimens and their side effects.

## Contribution

The paper provides a systematic review and meta-analysis of salvage regimens for EMA/CO-resistant GTN, offering evidence-based insights into treatment efficacy and safety.

## Key findings

- EMA/EP and EP/EMA regimens achieved a pooled complete remission rate of 78.7% in EMA/CO-resistant GTN.
- Neutropenia, thrombocytopenia, and anemia were the most common toxicities associated with EP/EMA.
- Alternative regimens like BEP, FAEV, and TP/TE showed promise but lack sufficient evidence for generalization.

## Abstract

This systematic review and meta-analysis evaluate the efficacy and safety of salvage regimens in managing EMA/CO-resistant GTN, providing evidence to inform optimal treatment strategies.

A literature search was conducted in PubMed, ScienceDirect, Cochrane Library, Google Scholar, and Wiley Online Library until December 27, 2024. Studies on EMA/CO chemoresistance in gestational trophoblastic neoplasia (GTN) were included, and alternative regimens and surgical interventions were also considered. Exclusion applied to non-human studies and those unrelated to EMA/CO chemoresistance. Data extraction and quality assessment followed PRISMA, Cochrane ROB-2, and the Newcastle-Ottawa Scale. A meta-analysis was performed using a random-effects model, with heterogeneity (I²) and publication bias assessed. The study was registered with PROSPERO (CRD42024574582).

Eight studies met the inclusion criteria, encompassing patients predominantly with advanced-stage (FIGO III-IV) and high-risk GTN. EMA/EP and EP/EMA were the most frequently evaluated salvage regimens, with a pooled complete remission rate of 78.7% (95% CI: 67.4–88.1%) across 84 patients. No significant heterogeneity (I² = 27.05%) or publication bias was detected. Alternative regimens, including BEP, FAEV, and TP/TE, demonstrated favourable remission rates in small cohorts but lacked generalizability. Neutropenia (68%), thrombocytopenia (41%), and anaemia (30%) were the most commonly reported toxicities with EP/EMA. Safety data for other regimens were limited.

EMA/EP and EP/EMA remain the most effective and well-studied salvage regimens for EMA/CO-resistant GTN, demonstrating high remission rates with manageable toxicity. While alternative regimens such as BEP, FAEV, and TP/TE show encouraging results, their limited evidence base precludes definitive comparison. Further prospective studies are needed to establish optimal salvage strategies and refine toxicity management.