Efficacy and Safety of Combining Gefitinib and Methotrexate in Treating Ectopic Pregnancy: A Systematic Review and Meta-Analysis

Background: Gefitinib is a tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR), mainly used for non-small cell lung cancer. Because EGFR is also highly expressed in placental tissue, its use has been explored in the treatment of ectopic pregnancy. This review examines the available evidence on the safety and effectiveness of combining gefitinib with methotrexate for the treatment of ectopic pregnancy. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive search was conducted across PubMed, Web of Science, ProQuest, and Google Scholar for English-language studies published between 2013 and 2023 comparing gefitinib plus methotrexate to methotrexate alone. Study quality was assessed using Joanna Briggs Institute (JBI) tools for quasi-experimental studies and case reports. Meta-analysis was performed using OpenMeta-Analyst with a random-effects model at a 0.05 significance level and 95% confidence intervals (CI). Results: Of 162 identified studies, five met the inclusion criteria, and three were included in the meta-analysis, comprising 526 participants. The pooled analysis revealed no statistically significant difference in complete resolution rates between the combination therapy group (69.3%) and the methotrexate-alone group (75.5%) (relative risks (RR): 1.004, 95% CI: 0.802–1.257; p = 0.973; I2 = 63.96%). Adverse events were generally mild and self-limiting, with rash (60.8%) and diarrhea (46.5%) being the most common. Serious adverse events were rare (<4%) and occurred at similar rates in both groups. Conclusions: These findings suggest that while the combination of gefitinib and methotrexate is safe, it does not significantly enhance treatment outcomes compared to methotrexate alone in managing ectopic pregnancy. Registration: The study has been registered on https://www.crd.york.ac.uk/prospero/ (registration number: CRD42024500567; registration link: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024500567).